Publications by authors named "Naser Tavakoli"

35 Publications

Simvastatin nanosuspensions prepared using a combination of pH-sensitive and timed-release approaches for potential treatment of colorectal cancer.

Pharm Dev Technol 2021 Mar 17;26(3):335-348. Epub 2021 Jan 17.

Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.

A dual pH- and time-dependent polymeric coated capsule was developed to achieve the site specificity of simvastatin (SIM) release in the colon. To improve the SIM solubility, soluplus-based nanosuspension of the drug were prepared by applying the anti-solvent crystallization technique; this was then followed by lyophilization. Particle size, polydispersity index, and saturation solubility were evaluated. The optimized nanosuspension was combined with SLS and freeze-dried before filling into hard gelatin capsules. Drug release characteristics of the coated capsules were studied in HCl 0.1 N, the phosphate buffers 6.8 and 7.4, and the simulated colonic fluid (pH 6.8). The cytotoxic effects of SIM nanoparticles against HT29 cells were then evaluated using the MTT assay. The prepared nanoparticles were spherical with a mean size of 261.66 nm, the zeta potential of -18.20 and the dissolution efficiency of 59.71%. X-ray diffraction and differential scanning calorimetry studies showed that the nanosizing technique transformed the crystalline drug into the more soluble amorphous form. The coated capsules had no release in the gastric media, providing the specific delivery of SIM in the colon. The cytotoxic effect of the SIM nanoparticles was significantly increased, as compared to the free SIM. The findings, therefore, showed that the coated capsules using the two polymers of ethyl cellulose and Eudragit S100 could be suitable for the colon target delivery of SIM.
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http://dx.doi.org/10.1080/10837450.2021.1872086DOI Listing
March 2021

In-vitro and in-vivo evaluation of chitosan-based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus.

IET Nanobiotechnol 2020 Apr;14(2):148-154

Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.

The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and β-glycerol phosphate (β-GP). The anticonvulsant efficacy of LZM-NLCs-Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of -20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β-GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in-vivo findings showed that compared with the control group and the group that received LZM-Gel, the occurrence of PTZ-induced seizures in the rats was significantly reduced by LZM-NLCs-Gel after intranasal administration. These results, therefore, suggested that the LZM-NLCs-Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.
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http://dx.doi.org/10.1049/iet-nbt.2019.0156DOI Listing
April 2020

An injectable carboxymethyl chitosan-methylcellulose-pluronic hydrogel for the encapsulation of meloxicam loaded nanoparticles.

Int J Biol Macromol 2020 May 3;151:220-229. Epub 2020 Feb 3.

Craniofacial and Cleft Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Hydrogel scaffolds have been frequently utilized due to their ability to absorb water and develop similar body cell conditions. Specific drug delivery to the tissues ensures less adverse side effects and more efficiency. In the present study, carboxymethyl chitosan (CMC)-methylcellulose (MC)-pluronic (P) and zinc chloride hydrogels containing meloxicam loaded into nanoparticles were developed and characterized. Nanoparticles were incorporated at 3.5, 4.5 and 5.5% (w/v). Hydrogels containing the same amounts of the meloxicam solution were also prepared. Gelation time, swelling and degradation of the hydrogels were investigated. Hydrogels were characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, and rheological analysis. Meloxicam release, chondrocytes attachment and growth on the hydrogels were also studied. Gelation time, swelling and the degradation rate of the hydrogels were found to be decreased by nanoparticles and increased with the addition of the meloxicam solution. SEM images also showed three-dimensional networks. The ATR-FTIR bands were shifted to the lower wave numbers in the hydrogels containing nanoparticles and shifted to the upper ones in the hydrogels containing meloxicam solution. Storage (G') and loss (G″) modulus were increased by the nanoparticles and reduced by the meloxicam solution. 100% of meloxicam was released from the hydrogels containing the meloxicam solution within 20 days, but it was released slowly from the hydrogels containing nanoparticles in 37days. Chondrocytes metabolic activity was increased on the 6th and 10th days for all hydrogels. Hydrogel containing nanoparticles showed good biocompatibility, bioadhesion, cell growth and expansion. The hydrogel could be, therefore, suitable as a new composite biomaterial for the regeneration of articular cartilage and meloxicam delivery to control the pain and inflammation in osteoarthritis.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.002DOI Listing
May 2020

Alginate hydrogel enriched with epidermal lipoxygenase-loaded pectin nanoparticles for enhanced wound healing.

J Biomater Appl 2020 03 30;34(8):1171-1187. Epub 2019 Dec 30.

Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery System Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

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http://dx.doi.org/10.1177/0885328219896704DOI Listing
March 2020

Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis.

Pharm Dev Technol 2019 Sep 4;24(7):891-901. Epub 2019 Jun 4.

b Department of Pharmaceutical Biotechnology, School of Pharmacy , Isfahan University of Medical Sciences , Isfahan , Iran.

This study was conducted to develop an thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the gel formulation. The cornea penetration of sertaconazole for the gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.
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http://dx.doi.org/10.1080/10837450.2019.1616755DOI Listing
September 2019

Formulation and Evaluation of Licorice Shampoo in Comparison with Commercial Shampoo.

J Pharm Bioallied Sci 2018 Oct-Dec;10(4):208-215

Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Aim: () or licorice with isoflavonoid, flavonoids, and triterpenoid glycosides (saponins) components are highly regarded in the cosmetic industry. This study has been planned as the first project for formulating a new herbal shampoo by utilizing the aqueous extracts of .

Materials And Methods: The dried powdered root of was extracted with boiled water through percolation method, and the pH was set by ammonia; then it was used with other constituents to formulate the herbal shampoo. The desirability of licorice shampoo was evaluated by physicochemical tests including visual inspection, detergency evaluation, pH assessment, percentage of solid contents, viscosity, foaming volume, and wetting time and compared with a commercial shampoo. Also, the product was checked for microbial control and consumers were asked about the quality of the licorice shampoo.

Results: The licorice shampoo has excellent cleansing ability, acceptable clarity, and viscosity. The volume of created foam and the wetting time were similar to the commercial shampoo. No microbial contamination was observed during the microbial control assessment tests. The licorice shampoo scored well on consumer's poll and was free from complication and also able to obviate hair and scalp problems.

Discussion And Conclusion: The results indicated that the consumers were satisfied with using the formulated licorice shampoo. Licorice shampoo seems to be helpful in obviation of hair problems, but specific investigations are required to prove this claim. The shampoo was safe from microbial contamination and showed acceptable results in physicochemical evaluations. Licorice shampoo could be useful in the treatment of many hair diseases, so further research is needed for discovering the potential of licorice shampoo.
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http://dx.doi.org/10.4103/JPBS.JPBS_243_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266641PMC
December 2018

Preparation and - evaluation of acyclovir floating tablets.

Res Pharm Sci 2017 Apr;12(2):128-136

Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Isfahan, I.R. Iran.

In the current study, floating dosage form containing acyclovir was developed to increase its oral bioavailability. Effervescent floating tablets containing 200 mg acyclovir were prepared by direct compression method with three different rate controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934, and Polyvinylpyrrolidone. Optimized formulation showed good floating properties and drug release characteristics with mean dissolution time and dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography exhibited that the tablet would reside in the stomach for about 5 ± 0.7 h. After oral administration of floating tablet containing 200 mg acyclovir, the , and AUC of optimized gastroretentive formulation were found to be 551 ± 141 ng/mL, 2.75 ± 0.25 h and 3761 ± 909.6 ng/mL/h, respectively.
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http://dx.doi.org/10.4103/1735-5362.202451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385727PMC
April 2017

Transdermal iontophoretic delivery of celecoxib from gel formulation.

Res Pharm Sci 2015 Sep-Oct;10(5):419-28

Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Celecoxib is used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, joint inflammation and sport injuries. Long term administration of the drug results in such complications as gastrointestinaland renal disturbances and cardio-vascular complications. The main objective of the present study was to investigate the feasibility of delivering celecoxib incorporated in gel formulations by iontophoresis. Sodium alginate, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC) and carbopol 934P were used to develop topical gel formulations of celecoxib. The gel formulations were evaluated for macroscopic and microscopic properties, pH determination, spreadability, rheological behaviour, and drug release characteristics both in vitro and ex vivo. Drug release was evaluated in the presence of iontophoresis field (0.1 to 0.5 mA/cm(2)) or without electrical current (passive diffusion) and celecoxib was measured spectrophotometrically at 252 nm. Most gel formulations showed acceptable physicochemical properties. Amongst formulations, gel formulation containing HPMC K4M which indicated greater performance in drug release behaviour was selected for further in vivo studies. The cumulative percent of drug released in vitro at the end of each experiment was 36%, 63%, and 89.7% for passive diffusion, direct electric current (DC) current density of 0.3 mA/cm(2), and 0.5 mA/cm(2), respectively. The findings of ex vivo drug transport across rat skin also showed a significantly higher release of celecoxib compared to passive flux for both AC and DC currents. A 0.5 mA/cm(2) of DC current increased drug flux to 73% compared to 41.5% of passive diffusion. It can be concluded from the results of this study that the application of iontophoresis enhances the flux of celecoxib, as compared to the passive diffusion.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691962PMC
January 2016

The efficacy of Achilles millefolium topical gel along with intralesional injection of glucantime in the treatment of acute cutaneous leishmaniasis major.

Adv Biomed Res 2014 31;3:111. Epub 2014 Mar 31.

Department of Pharmacology, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Leishmaniasis is still one of the endemic parasitic infections in many countries comprising Iran. During the past decades, several medical and surgical approaches have been applied and studied to achieve the best option to treat the cutaneous leishmaniasis in Iran and the world. This study was carried out to evaluate the effect of topical Achilles millefolium in conjunction with intralesional glucantime on acute cutaneous leishmanial lesions.

Materials And Methods: sixty patients with confirmed acute cutaneous leishmaniasis were recruited in the study. Patients were randomly allocated into two groups to receive twice daily topical gel of Achilles millefolium 5% (containing 5% poly phenol) (group A) or placebo (group B) for four weeks along with weekly injection of intralesional Glucantime.

Results: There was no significant difference between the two groups according to age, gender, and duration of the disease. Also, there was no significant difference in complete and relative cure rates between the two groups (P = 0.35) using Visual Analog Scale (VAS). Application site reactions were occurred in 12 patients including redness in 8 cases in group-A and 2 cases in group-B, severe itching in one case in group-A and increasing wound secretion in another case in group-A (P = 0.014).

Conclusions: Given the result of the present study, there is no significant difference in cure rates of lesions between yarrow and placebo topical gels as an adjuvant drugs with intralesional glucantime in treatment of acute cutaneous leishmanial lesions.
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http://dx.doi.org/10.4103/2277-9175.129717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009745PMC
May 2014

Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

J Microencapsul 2014 3;31(6):529-34. Epub 2014 Apr 3.

Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center and.

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.
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http://dx.doi.org/10.3109/02652048.2014.885604DOI Listing
May 2015

Transfection and structural properties of phytanyl substituted gemini surfactant-based vectors for gene delivery.

Phys Chem Chem Phys 2013 Dec 1;15(47):20510-6. Epub 2013 Nov 1.

School of Pharmacy, University of Waterloo, Ontario, 10 Victoria Str. S. Kitchener, ON, Canada.

In this study, the transfection ability and cytotoxicity of a series of phytanyl substituted gemini surfactants, rationally designed and synthesized in an attempt to create cationic surfactants that will improve transfection efficiencies of non-viral vectors was evaluated in OVCAR-3 cells at the charge ratios (N(+)/P(-)) of 2:1, 5:1, and 10:1. Particle sizes, zeta potentials, and small angle X-ray scattering (SAXS) profiles were also determined. For each gemini surfactant complex, the transfection efficiency and cytotoxicity are observed to go through a more or less well-evidenced maximum, occurring at different values of the charge ratio (N(+)/P(-)), depending on the surfactant structure. Considering both results of in vitro transfection efficiency and cytotoxicity, the optimal charge ratio to formulate the complexes containing phy-3-m was found to be 5:1. The particle size decreased, while zeta potential increased with increasing N(+)/P(-). Comparing particle size and zeta potential with transfection efficiency, no correlation between size/zeta potential and transfection ability was observed. Analysis of SAXS profiles indicates that the ability of phy-3-m delivery system to adopt multiple phases correlated well with their higher transfection efficiency in OVCAR-3 cells.
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http://dx.doi.org/10.1039/c3cp52621fDOI Listing
December 2013

The effect of Boswellia Serrata on neurorecovery following diffuse axonal injury.

Brain Inj 2013 2;27(12):1454-60. Epub 2013 Oct 2.

Behavioral Sciences Research Center, Noor Hospital, Isfahan University of Medical Sciences , Isfahan , Iran .

Objectives: This pilot trial was conducted to establish whether Boswellia Serrata (BS), a traditional herbal medicine, could improve the outcome of patients who have diffuse axonal injury (DAI).

Methods: In total, 38 patients with pure DAI were enrolled in this 12-week, double-blind, randomized, cross-over study. The patients were randomly assigned to receive either placebo (group A, n = 20) or BS capsules (group B, n = 18) for 6 weeks and then switched to the other intervention for another 6 weeks. The disability rating scale (DRS) was used to assess the outcome at 2-, 6- and 12-weeks post-trauma.

Results: A non-significant trend for improvement of DRS total scores was observed after the use of BS. Regarding the DRS sub-scores, however, there was significant improvement in 'cognitive ability to self-care' during the second 6 weeks in group A on BS compared to an insignificant spontaneous recovery in group B during the same period on placebo. Moreover, both groups experienced a close-to-significant increase in the cognitive function-related items of the DRS during the periods they were on BS. The reported adverse events were all of mild quality and had similar frequency between the groups.

Conclusion: These results suggest that BS resin does not significantly affect general outcome, but may enhance the cognitive outcome of patients with DAI.
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http://dx.doi.org/10.3109/02699052.2013.825009DOI Listing
June 2014

Colon specific delivery of budesonide based on triple coated pellets: in vitro/in vivo evaluation.

Acta Pharm 2012 Nov;62(3):341-56

Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Three layered pellets of budesonide were prepared for colon delivery by the extrusion-spheronization method. The coatings consisted of hydroxypropylmethyl cellulose (HPMC) (as barrier layer), Eudragit E (as rate controlling layer) and hydroxypropylmethyl cellulose acetate succinate (HPMC AS) (as enteric layer). The rate controlling layer was further modified using various pore formers. Dissolution studies were carried out at pH 1.2, 7.4 and 6.8. Pellet core composition and type and level of pore former affected the drug release from pellets. Pellets containing 20% (m/m) citric acid in the cores coated with HPMC at a coating level of 6% (m/m), Eudragit E containing Avicel RC 581 (30%) as pore former at a coating level of 30% (m/m) and HPMC AS at a coating level of 15% (m/m) had the best release profiles. These pellets showed promising results in alleviating the conditions of an experimental model of colitis induced by trinitrobenzenesulfonic acid in rats.
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http://dx.doi.org/10.2478/v10007-012-0025-yDOI Listing
November 2012

Pectin Film Coated Pellets for Colon-targeted Delivery of Budesonide: In-vitro/In-vivo Evaluation in Induced Ulcerative Colitis in Rat.

Iran J Pharm Res 2012 ;11(3):733-45

Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery System Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

The main objective of this study was to prepare colon-specific pellets of budesonide, using pectin as film coating. Pellet cores of budesonide were prepared by extrusion / spheronization technique. Pectin, in different ratios was combined with Eudragit RS30D, Eudragit NE30D or Surelease to produce film coating. The dissolution profiles of pectin coated pellets were investigated in pH of 1.2 (2 h), pH of 7.4 (4 h) and pH of 6.8 in the absence as well as presence of rat cecal contents (18 h). Finally the selected formulation was evaluated on trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rat model, in comparison with conventional UC treatments. The dissolution profiles of pectin coated pellets showed that the release of budesonide in presence of rat cecal content depended on adjuvant polymer, the ratio of pectin to polymer and film thickness. Coated pellets, prepared out of pectin and Surelease at a ratio of 1:3 at coating level of 35% (w/w), could increase budesonide release statistically in presence of rat cecal content, while they released no drug in pH of 1.2 and 7.4. Animal experiments revealed the therapeutic efficacy of pectin/Surelease-coated pellets of budesonide in alleviating the conditions of TNBS-induced colitis model as reflected by weight gain, as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis. This confirmed the ability of the optimized formulation for targeted drug delivery of budesonide to colon.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813129PMC
November 2013

Development and evaluation of a novel pellet-based tablet system for potential colon delivery of budesonide.

J Drug Deliv 2012 22;2012:905191. Epub 2012 Apr 22.

Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.

Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3 : 7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24 h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets.
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http://dx.doi.org/10.1155/2012/905191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346988PMC
August 2012

Mixed aggregate formation in gemini surfactant/1,2-dialkyl-sn-glycero-3-phosphoethanolamine systems.

J Colloid Interface Sci 2012 Jul 5;377(1):237-43. Epub 2012 Apr 5.

School of Pharmacy, University of Waterloo, 10 Victoria Str. S., Kitchener, ON, Canada N2G 1C5.

An evaluation of the physical interactions between gemini surfactants, DNA, and 1,2-dialkyl-sn-glycero-3-phosphoethanolamine helper lipid is presented in this work. Complexation between gemini surfactants and DNA was first investigated using surface tensiometry where the surface tension profiles obtained were found to be consistent with those typically observed for mixed surfactant-polymer systems; that is, there is a synergistic lowering of the surface tension, followed by a first (CAC) and second (CMC) break point in the plot. The surfactant alkyl tail length was observed to exhibit a significant effect on the CAC, thus demonstrating the importance of hydrophobic interactions during complexation between gemini surfactants and DNA. The second study presented is an investigation of the mixing interactions between gemini surfactants and DOPE using Clint's, Rubingh's, and Motomura's theories for mixed micellar formation. The mixing interactions between the 16-3-16/16-7-16/16-12-16/16-7NH-16 gemini surfactants and DOPE were observed to be antagonistic, where the strength of antagonism was found to be dependent upon the gemini surfactant spacer group and the solution composition.
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http://dx.doi.org/10.1016/j.jcis.2012.03.048DOI Listing
July 2012

Development and evaluation of a monolithic floating drug delivery system for acyclovir.

Chem Pharm Bull (Tokyo) 2012 ;60(2):172-7

Department of Pharmaceutics, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200 mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1 N HCl (pH 1.2) at 37±0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ(max)=259 nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30 s and a duration of floating time of 24 h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.
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http://dx.doi.org/10.1248/cpb.60.172DOI Listing
June 2012

Development and evaluation of a monolithic floating drug delivery system for acyclovir.

Chem Pharm Bull (Tokyo) 2012 ;60(2):172-7

Department of Pharmaceutics, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200 mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1 N HCl (pH 1.2) at 37±0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ(max)=259 nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30 s and a duration of floating time of 24 h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.
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http://dx.doi.org/10.1248/cpb.60.172DOI Listing
June 2012

Effect of fluoridated dentifrices on surface microhardness of the enamel of deciduous teeth.

Dent Res J (Isfahan) 2011 ;8(3):113-7

Associate Professor, Pediatric Dentistry Department and Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Surface microhardness is a physical property which access the effect of chemical and physical agents on hard tissues of teeth, and a useful way to examine the resistance of fluoride treated enamel against caries. The purpose of this study was to evaluate microhardness of enamel following pH-cycling through demineralization and remineralization using suspensions of dentifrices with different fluoride contents.

Methods: In this in vitro study 56 enamel blocks of primary incisors were soaked in demineralizing solution and four dentifrices suspensions including: Crest 1100 ppm F (NaF), Crest 500 ppm F (NaF), Pooneh 500 ppm F (NaF,) and Pooneh without fluoride. The means and percentage changes of surface microhardness in pre-demineralization, after demineralization and remineralization stages in four groups were measured. The findings of four groups in three stages were compared by, ANOVA, Tukey and paired t-tests. (α=0.05)

Results: Average surface microhardness changes of Crest 1100 ppm F, was higher than Crest 500 ppm F, Pooneh 500 ppm F, and Pooneh without fluoride. The percentages of surface microhardness recovery for Crest 1100 ppm F, Crest 500 ppm F, Pooneh 500 ppm F, and Pooneh without fluoride were 45.4, 35.4, 28.6, and 23.7 respectively. Demineralization treatment decreased the surface microhardness of enamel (P<0.05) and the surface microhardness recovery in all groups were significant (P<0.0001).

Conclusion: Surface microhardness of enamel after remineralization by Crest 1100 ppm F was higher than Crest 500 ppm F, Pooneh 500 ppm F, and Pooneh without fluoride.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177384PMC
November 2011

Colon delivery of budesonide using solid dispersion in dextran for the treatment and secondary prevention of ulcerative colitis in rat.

Int J Prev Med 2010 ;1(2):115-23

Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Centre, Isfahan University of Medical Sciences (IUMS), Isfahan, Iran.

Objectives: Ulcerative colitis is characterized by local inflammation. Targeting drugs directly to the site of injury has the benefit of lower adverse effects and more effective therapy. The aim of this study was colon targeted delivery of budesonide to deliver the major part of the drug to the colon.

Methods: Matrix tablets of budesonide from solid dispersion of drug with dextran were prepared using different drug to polymer ratios and three molecular weights of dextran. The physical evaluation and drug release behavior were studied. In vivo efficacy of the selected formulation against acetic acid induced colitis in rats was evaluated and compared to the control (untreated) and references (mesalazine and budesonide suspensions) groups.

Results: The results showed that solid dispersion of budesonide with dextran in the ratio of 1:7 using molecular weight (MW) of 10,000 dextran (SDT710) released 25% of the drug in the first 6 hours and 100% in caecal and colonic contents. It could target the drug to colon with improvement in some of the inflammatory signs of induced ulcerative colitis in rat. Treatment with SDT710 could improve not only the percent of involvement also macroscopic damage parameters. The macroscopic parameters included weight/length ratio of the colon, ulcer area, damage score, and ulcer index reduced in comparison to the control group and conventional suspension of budesonide; however, only weight/length ratio was significant.

Conclusions: In the experimental model studied, the new colonic delivery system significantly improved the efficacy of budesonide in the weight/length ratio of the colon in induced colitis in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075473PMC
July 2011

Microencapsulation of budesonide with dextran by spray drying technique for colon-targeted delivery: an in vitro/in vivo evaluation in induced colitis in rat.

J Microencapsul 2011 ;28(1):62-73

Department of Pharmaceutics and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

The aim of this study was developing colon targeted-delivery of budesonide for ulcerative colitis. Microcapsules were prepared using spray drying technique by different drug-to-dextran ratios and three molecular weights (MWs) of polymer. Differential scanning calorimetry, X-ray diffraction (XRD), drug release and loading efficiency of microcapsules were studied. In vivo efficacy of the selected formulation prepared by 1 : 10 drug-to-polymer ratio and dextran with MW 500 000 (D10M500) against acetic acid-induced colitis in rats was evaluated and compared to the control and reference groups (mesalasine and budesonide suspensions). The results showed that D10M500 microcapsules could target the drug to colon and its efficacy in reducing macroscopic damage score was higher than mesalasine suspension. Treatment with D10M500 decreased the scores of crypt damage and total colitis significantly compared to the control group which just received the vehicle and the groups treated with mesalasine and budesonide suspension which could not reduce the colitis parameters significantly.
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http://dx.doi.org/10.3109/02652048.2010.529947DOI Listing
April 2011

A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity.

World J Pediatr 2010 Nov 16;6(4):317-22. Epub 2010 Nov 16.

Isfahan Endocrine & Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The efficacy of pharmacological treatment in controlling childhood obesity is controversial. We aimed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification (diet and exercise).

Methods: This triple-masked randomized clinical trial was conducted among 180 participants aged 10-16 years. They were assigned randomly to 4 groups of equal number to receive metformin, fluoxetine, a combination of the two drugs, or placebo. The trial lasted for 12 weeks and participants were followed up for an additional 12-week period.

Results: Overall, 91.1% (n=164) of the enrolled participants completed the trial. After the 12-week trial, the body mass index decreased significantly in all groups receiving medications [approximately -1.2 (0.2) kg/m², P<0.05]. This decrease was not significant in the placebo group. Waist circumference decreased significantly in the groups receiving metformin [-2.1 (0.4) cm, P=0.03)] as well as in the group receiving a combination therapy of metformin and fluoxetine [-2.5 (0.4) cm, P=0.01)]. In the 24-week follow-up study, these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine. No serious drug side-effects were reported.

Conclusions: A limited period of such treatment may help weight control, and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs. Our findings should be confirmed in future studies with a longer follow-up period.
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http://dx.doi.org/10.1007/s12519-010-0232-xDOI Listing
November 2010

Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome.

Metab Syndr Relat Disord 2010 Dec 28;8(6):505-10. Epub 2010 Oct 28.

Department of Pediatric Preventive Cardiology, Isfahan Cardiovascular Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Objective: This trial aimed to evaluate the effects of zinc sulfate in comparison with placebo on markers of insulin resistance, oxidative stress, and inflammation in a sample of obese prepubescent children.

Methods: This triple-masked, randomized, placebo-controlled, crossover trial was conducted among 60 obese Iranian children in 2008. Participants were randomly assigned to two groups of equal number; one group received 20  mg of elemental zinc and the other group received placebo on a regular daily basis for 8 weeks. After a 4-week washout period, the groups were crossed over. In addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A-1 (ApoA-I) and B, high-sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde were determined at all four stages of the study.

Results: Irrespective of the order of receiving zinc and placebo, in both groups, significant decrease was documented for Apo B/ApoA-I ratio, ox-LDL, leptin and malondialdehyde, total and LDL-cholesterol after receiving zinc without significant change after receiving placebo. In groups, hs-CRP and markers of insulin resistance decreased significantly after receiving zinc, but increased after receiving placebo. In both groups, the mean body mass index (BMI) Z-score remained high, after receiving zinc, the mean weight, BMI, BMI Z-score decreased significantly, whereas these values increased after receiving placebo.

Conclusion: These results are particularly important in light of the deleterious consequences of childhood obesity and early changes in markers of inflammatory and oxidative stress. We suggest exploring the direct clinical application of zinc supplementation in childhood obesity in future studies.
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http://dx.doi.org/10.1089/met.2010.0020DOI Listing
December 2010

Preparation and in vitro/in vivo evaluation of dextran matrix tablets of budesonide in experimental ulcerative colitis in rats.

Drug Deliv 2011 Feb 18;18(2):122-30. Epub 2010 Oct 18.

Isfahan University of Medical Sciences, Isfahan, Iran.

Budesonide is an anti-inflammatory drug of choice for treatment of ulcerative colitis which affects the rectum and a part of or the entire colon. Delivery of budesonide specifically to the colon would increase the efficacy of the drug and reduce the side-effects. The aim of this study was to develop an oral matrix system formulation for budesonide to deliver the major part of the drug to the colon for treatment of ulcerative colitis that has not been reported before. Directly compressed matrix tablets were prepared using different molecular weights of dextran and three ratios of drug-to-polymer. The physical properties of the tablets including weight variation, hardness, content uniformity, and release profile in HCl 0.1 N, phosphate buffer pH 7.4 and 6.8 containing 4% rat caecal and colonic contents were studied. The efficacy of the desired formulation was also evaluated against acetic acid-induced colitis in rats. Physical properties of the tablets were in the ranges recommended by official references. More than 10% of the drug was released in HCl 0.1 N and pH 7.4, while a very drastic increase was observed after exposure to pH 6.8 containing rat caecal contents. The efficacy of the selected formulation against rat-induced colitis was also increased in comparison to the non-targeted formulation of budesonide. In conclusion, matrix tablets with a 1:10 drug-to-dextran ratio with high molecular weight could deliver the drug specifically to the colon and are promising for treatment of ulcerative colitis.
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http://dx.doi.org/10.3109/10717544.2010.520352DOI Listing
February 2011

Enhanced dissolution rate of simvastatin using spherical crystallization technique.

Pharm Dev Technol 2011 Oct 5;16(5):529-35. Epub 2010 Aug 5.

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Simvastatin is a hypocholestrolemic drug that is insoluble in water. Its low water solubility rate limits the pharmacological effects. The aim of this study was to improve the dissolution rate of simvastatin using spherical crystallization method. The drug was dissolved in boiling dichloromethane as the good solvent. This solution was added to 5°C water as the non-solvent. After sedimentation, isopropyl acetate was added as the bridging solvent. At the end the crystals were collected and dried for 12 h in a 50°C oven. The FTIR and DSC results showed no change in the drug after crystallization process. XRPD studies showed the sharp peaks are present in the diffractograms of spherical crystals with minor reduction in height of the peaks. The particle size of spherical aggregates was about 37 μm and the dissolution efficiency of simvastatin up to 60 min increased to about 2-fold in phosphate buffer solution containing 0.5% sodium dodecyl sulfate (pH 7) using the rotating paddle method. Spherical crystals showed enhanced solubility than untreated powder possibly due to partial conversion to amorphous form. Their dissolution rate at 60 min was still 4-fold of untreated powder when stored at 25°C and 84% relative humidity for one month.
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http://dx.doi.org/10.3109/10837450.2010.502175DOI Listing
October 2011

Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats.

Int J Colorectal Dis 2010 Oct 29;25(10):1159-65. Epub 2010 Jul 29.

Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Anti-inflammatory drugs with high potency and low systemic adverse effects, such as budesonide, are drugs of choice for the treatment of ulcerative colitis (UC). Budesonide controlled-release formulations are now being used to induce and maintain clinical remission of Crohn's disease. Budesonide-dextran conjugates were synthesized as novel prodrugs of budesonide for oral controlled delivery of the major part of the drug to the colon without needing to coat the pellets of the drug. The aim of this study was to evaluate the in vivo efficacy of this conjugate against acetic acid-induced colitis in rats.

Materials And Methods: Experimental UC was induced by rectal instillation of 4% solution of acetic acid to rats. After induction of colitis, rats were treated with vehicle (dextran solution), mesalasine (120 mg/kg), budesonide suspension (300 microg/kg) and BSD-70 (equivalent to 300 microg/kg of budesonide), prednisolon (4 mg/kg), hydrocortisone acetate enema (20 mg/kg), and 5-ASA enema (Asacol) (400 mg/kg) for 5 days and then colon macroscopic and microscopic sections were examined for inflammatory response.

Results: Vehicle-treated rats presented bloody diarrhoea and gross lesions. The effective formulations for attenuating the damage were BSD-70, oral prednisolon and hydrocortisone acetate enema. Rats treated with BSD-70 showed huge improvement in macroscopic and histological scores of colitis compared to the negative control group and mesalasine and budesonide suspension.

Conclusion: Data indicated that budesonide-dextran conjugate is effective in improving signs of inflammation in experimental model of colitis through selective delivery of the drug to the inflamed area.
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http://dx.doi.org/10.1007/s00384-010-1026-2DOI Listing
October 2010

Preparation of budesonide-dextran conjugates using glutarate spacer as a colon-targeted drug delivery system: in vitro/in vivo evaluation in induced ulcerative colitis.

J Drug Target 2011 Feb 30;19(2):140-53. Epub 2010 Apr 30.

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

An oral colon-targeted formulation of budesonide was developed for treatment of ulcerative colitis. Budesonide conjugates were prepared using glutarate spacer and different molecular weights (MW) of dextran and their degree of substitution (DS), solubility, and stability were examined. Drug release in the presence of rat colonic contents was studied. In vivo efficacy was studied against acetic-acid induced colitis in rat. DS was dependent on polymer MW and was 7.40 ± 0.18, 5.20 ± 0.35, and 13.80 ± 0.48 mg/100 mg conjugate for MW 10,000, 70,000, and 500,000, respectively. Solubility of drug in conjugates of MW 10,000 and 70,000 was increased and was dependent on DS. The conjugates were stable in HCl 0.1 N, phosphate buffer solutions pH 6.8, and 7.4 incubated at 37°C within 6 h and degradation rate constants were <0.009 h(-1). Less than 10% of budesonide was released in contents of stomach and small intestine and it was increased significantly after incubating with colonic contents. The conjugate prepared using dextran 70,000 was selected for in vivo studies that could decrease the macroscopic and microscopic scores of induced colitis compared with mesalasine and budesonide suspension.
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http://dx.doi.org/10.3109/10611861003801826DOI Listing
February 2011

Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children.

Hormones (Athens) 2009 Oct-Dec;8(4):279-85

Isfahan Endocrine & Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Objective: Zinc, an essential trace element and a component of many enzymes, is involved in the synthesis, storage and release of insulin. The aim of the present study was to assess the effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children.

Design: This triple-masked, randomized, placebo-controlled cross-over trial was conducted among 60 obese Iranian children in 2008. Pertinent clinical findings, fasting serum glucose, insulin and lipid profile were assessed. Participants were randomly assigned to two groups of equal number; one group received 20mg elemental zinc and the other group received placebo on a regular daily basis for eight weeks. After a 4-week wash-out period, the groups were crossed over.

Results: The mean age of participants was 9.1 +/- 1.1 years. After receiving zinc, the mean fasting plasma glucose (FPG), insulin and HOMA-IR decreased significantly, while body mass index (BMI), waist circumference (WC), LDL-C and triglycerides (TG) did not significantly change. After receiving placebo, the mean FPG, insulin and HOMA-IR increased significantly, while BMI, WC, LDL-C and TG showed a non-significant increase.

Conclusion: Besides lifestyle modification, zinc supplementation might be considered as a useful and safe additional intervention treatment for improvement of cardiometabolic risk factors related to childhood obesity.
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http://dx.doi.org/10.14310/horm.2002.1244DOI Listing
February 2010

Preparation and in vitro characterization of piroxicam enteric coated pellets using powder layering technique.

Pharm Dev Technol 2009 ;14(3):305-11

Department of Pharmaceutics, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran.

The objective of this study was to develop piroxicam enteric coated pellets using nonpareil seeds by powder layering technique to minimize its gastrointestinal adverse effects. Inert seeds were prepared by incorporating sugar, Avicel PH 101 and lactose. The obtained cores were then treated by PVP 10 w/v % solution using centrifugal granulator (CF-granulator) and then coated with micronized piroxicam using HPMC solution (8 w/v %) as binder. The piroxicam pellets were finally coated with different polymers (Eudragit L30D-55, Eudragit L100, Eudragit NE30D, Acryleze, or mixture of Eudragits L30D-55 and NE30D) and plasticizers (triethyl citrate and polyethylene glycol 6000). Results showed that Eudragit L30D-55 with 3% weight gain accompanied with TEC produced suitable enteric coated pellets.
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http://dx.doi.org/10.1080/10837450802626288DOI Listing
October 2010

Synthesis and evaluation of dextran-budesonide conjugates as colon specific prodrugs for treatment of ulcerative colitis.

Int J Pharm 2009 Jan 30;365(1-2):69-76. Epub 2008 Aug 30.

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Budesonide is a potent glucocorticoid with high affinity for the glucocorticoid receptor, which is now used for the treatment of inflammatory bowel diseases. Current oral formulations of budesonide present low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. The objective of this study was to develop a colon specific delivery system for budesonide to increase the efficacy in the treatment of ulcerative colitis. Dextran-budesonide conjugates were prepared with different molecular weights (MW) of dextran (10,000, 70,000 and 500,000) in the presence of dimethylaminopyridine (DMAP) using succinate spacer. The conjugates were characterized by (1)H NMR and IR spectroscopy and elemental analysis. The degree of substitution, aqueous solubility and chemical stability of conjugates in HCl 0.1N, phosphate buffer solutions pH 6.8 and 7.4 were studied. Drug release characteristics of the conjugates were also studied in the presence of the luminal contents of different segments of the rat gastrointestinal tract. Degree of substitution (DS) was dependent on the polymer MW and was 19.33, 14.29 and 11.60 mg/100 mg conjugate for MW 10,000, 70,000 and 500,000, respectively. Solubility of the drug in conjugates of MW 10,000 and 70,000 was increased with respect to the free drug and was dependent on DS. The three conjugates were found to be stable in HCl 0.1N, phosphate buffer solutions pH 6.8 and 7.4 incubated at 37 degrees C within 6 h and the rate constants for degradation of conjugates to budesonide and budesonide hemisuccinate were less than 0.006 h(-1). Less than 10% of the drug was released in contents of the stomach and small intestine, while about two-fold increase was observed after incubating the conjugates with colonic luminal contents. Conjugate prepared by dextran 70,000 showed the most desirable solubility, stability and release properties and could therefore be evaluated in vivo, for potential clinical use in the treatment of ulcerative colitis.
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http://dx.doi.org/10.1016/j.ijpharm.2008.08.034DOI Listing
January 2009