Publications by authors named "Mosab Arafat"

13 Publications

  • Page 1 of 1

Development and In Vitro Evaluation of Controlled Release Viagra Containing Poloxamer-188 Using Gastroplus PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments.

Pharmaceuticals (Basel) 2021 May 18;14(5). Epub 2021 May 18.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates.

Sildenafil is the active substance in Viagra tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix system with the aim to improve solubility, control the drug release, and sustain the duration of drug activity. The controlled release matrices were prepared with poloxamer-188, hydroxypropyl methylcellulose, and magnesium stearate. Various formulations of different ratios were developed, evaluated in vitro, and assessed in silico. Poloxamer-188 appeared to have a remarkable influence on the release profile of sildenafil citrate. In general, the rate of drug release decreased as the amount of polymer was gradually increased in the matrix system, achieving a maximum release period over 12 h. The in silico assessment by using the GastroPlus™ PBPK modeling software predicted a significant variation in C t, t, and AUC among the formulations. In conclusion, the combination of polymers in matrix systems can have substantial impact on controlling and modifying the drug release pattern.
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http://dx.doi.org/10.3390/ph14050479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158482PMC
May 2021

Comparison between Branded and Generic Furosemide 40 mg Tablets Using Thermal Gravimetric Analysis and Fourier Transform Infrared Spectroscopy.

J Pharm Bioallied Sci 2020 Oct-Dec;12(4):489-498. Epub 2020 Oct 8.

College of Medicine and Health Sciences, The United Arab Emirates University, Al Ain, UAE.

Background And Purpose: There has been a long-standing belief that generic drugs are of lower value in comparison to their branded name counterparts. They are in particular under scrutiny due to their low market price. Even though the reduction in costs is largely based on skipping expensive preclinical studies and clinical trials for generic drugs, the purity and quality of the raw materials in the production of generic drugs is debatable. Thus, the objective of the study was to analyze and assess the quality comparability of generic furosemide 40 mg (FSD) tablets to branded product available in the market.

Materials And Methods: Quality control tests, in vitro drug release assessments, and thermal analysis investigations for both analog products of FSD were performed. Various physical parameters related to the tablet quality, such as hardness, weight variation, and friability tests, were examined. In vitro drug release behavior evaluations were conducted according to United States Pharmacopeia (USP) specifications and guidelines, whereas thermal analysis was carried out using thermal gravimetric analysis (TGA), and tablets were further evaluated by Fourier transform infrared (FTIR) spectroscopy.

Results: The results indicated a significant variation between the two products in terms of hardness, weight variation, and friability. This could be correlated to variation appeared in thermal and spectroscopic spectra between the two products using TGA and FTIR. Drug release of FSD was slightly different between both products following incubation in different pH media (1.2, 3.0, and 6.5; 120 min), however, this was in accordance with USP dissolution requirements as < 80% of drug release was obtained within the first 30 min from each product.

Conclusion: This study is a useful example for the independent investigations using thermal and spectroscopic analysis to confirm potential hidden variations between generic and branded products that could not be obtained by the bioequivalence studies.
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http://dx.doi.org/10.4103/jpbs.JPBS_365_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909057PMC
October 2020

Prediction of lisinopril pediatric dose from the reference adult dose by employing a physiologically based pharmacokinetic model.

BMC Pharmacol Toxicol 2020 07 29;21(1):56. Epub 2020 Jul 29.

Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.

Background: This study aimed to assess the pediatric lisinopril doses using an adult physiological based pharmacokinetic (PBPK) model. As the empirical rules of dose calculation cannot calculate gender-specific pediatric doses and ignores the age-related physiological differences.

Methods: A PBPK model of lisinopril for the healthy adult population was developed for oral (fed and fasting) and IV administration using PK-Sim MoBI® and was scaled down to a virtual pediatric population for prediction of lisinopril doses in neonates to infants, infants to toddler, children at pre-school age, children at school age and the adolescents. The pharmacokinetic parameters were predicted for the above groups at decremental doses of 20 mg, 10 mg, 5 mg, 2.5 mg, and 1.5 mg in order to accomplish doses producing the pharmacokinetic parameters, similar (or comparable) to that of the adult population. The above simulated pediatric doses were compared to the doses computed using the conventional four methods, such as Young's rule, Clark's rule, and weight-based and body surface area-based equations and the dose reported in different studies.

Results: Though the doses predicted for all subpopulations of children were comparable to those calculated by Young's rule, yet the conventional methods overestimated the pediatric doses when compared to the respective PBPK-predicted doses. The findings of previous real time pharmacokinetic studies in pediatric patients supported the present simulated dose.

Conclusion: Thus, PBPK seems to have predictability potential for pediatric dose since it takes into consideration the physiological changes related to age and gender.
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http://dx.doi.org/10.1186/s40360-020-00429-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389632PMC
July 2020

Impact of pharmacist interventions on drug-related problems in general surgery patients: a randomised controlled trial.

Eur J Hosp Pharm 2020 Jul 13. Epub 2020 Jul 13.

College of Pharmacy, Al Ain University, Al Ain, Abu Dhabi, United Arab Emirates.

Objectives: The inappropriate use of medications is harmful and is a common issue in hospitalised patients. Patients hospitalised in general surgery wards are usually at high risk for drug-related problems (DRPs). This randomised controlled trial aimed to explore the value of a pharmaceutical care service conducted in general surgery wards in the identification and reduction of DRPs in comparison with standard medical care.

Methods: This study was conducted in general surgery wards including abdominal, cardiovascular, vascular, endocrine, orthopaedic and oncological surgeries at one of the largest teaching hospitals in Jordan over a period of 6 months. Recruited patients were randomised into intervention or control groups. Clinical pharmacists assessed patients' DRPs and submitted recommendations to resolve the identified DRPs in the intervention group.

Results: Patients in the intervention group (n=63) and the control group (n=60) had a mean age of 55±14.4 years, with 52.0% being women. A total of 1062 DRPs were identified, with a mean of 8.6±3.6 per patient (intervention group, 8.65±4.2; control group, 8.62±2.6; p=0.56). The commonly identified DRPs included safety (20.2%) and efficacy (19.0%) issues. The acceptance rate for pharmacists' recommendations by physicians was very high (90%) with a good DRP correction rate of 58.9% during patients' hospital stay. The value of pharmaceutical care was significantly reflected in the achievement of the therapeutic outcomes and prevention of morbidity (resolved/improved or prevented) of 68.2% (24.2%+44%) in the intervention group compared with 19.2% (12.4%+6.8%) in the control group (p<0.001).

Conclusions: This study shows that DRPs are common among general surgery patients in Jordan, especially those related to drug safety and efficacy. Pharmacists' recommendations contributed substantially to resolving most of the identified DRPs and had a significant impact on improving medications used in general surgery patients.
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http://dx.doi.org/10.1136/ejhpharm-2020-002206DOI Listing
July 2020

Transdermal patches: Design and current approaches to painless drug delivery.

Acta Pharm 2019 Jun;69(2):197-215

Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine The Islamia University of Bahawalpur Pakistan.

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.
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http://dx.doi.org/10.2478/acph-2019-0016DOI Listing
June 2019

Butylglyceryl Pectin Nanoparticles: Synthesis, Formulation and Characterization.

Polymers (Basel) 2019 May 2;11(5). Epub 2019 May 2.

School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, Portsmouth PO1 2DT, UK.

Pectin is a polysaccharide with very good gel forming properties that traditionally has found important applications in foods and pharmaceutical industries. Although less studied, chemical modifications of pectin leading to a decrease in its hydrophilicity can be useful for the development of novel drug carriers. To this aim, butylglyceryl pectins (P-OX4) were synthesized via functionalization with -butylglycidyl ether and subsequently formed into nanoparticles. Chromatographic, spectroscopic, and thermal analytical methods were employed to characterize the novel butylglyceryl pectins (P-OX4) obtained, prior to their formulation into nanoparticles via nanoprecipitation. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy confirmed a degree of modification in these materials in the range 10.4-13.6%, and thermal stability studies indicated an increase in both the thermal decomposition onset and glass transition temperature values (compared to those of the original pectin). An increase in the molecular weight and a decrease in the viscosity of P-OX4, when compared to the starting material, were also observed. The resulting nanoformulations were investigated in terms of particle morphology, size and stability, and it was found that particles were roughly spherical, with their size below 300 nm, and a negative zeta potential (-20 to -26 mV, indicating good stability). Having demonstrated the ability to load Doxorubicin at the level of 10%, their potential in drug delivery applications warrants further investigations.
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http://dx.doi.org/10.3390/polym11050789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571649PMC
May 2019

Capacity and willingness to use information technology for managing chronic diseases among patients: A cross-sectional study in Lahore, Pakistan.

PLoS One 2019 10;14(1):e0209654. Epub 2019 Jan 10.

Department of Pharmacy Practice, Akhtar Saeed College of Pharmaceutical Sciences, Lahore, Punjab, Pakistan.

Background And Objectives: The information technology is a pivotal source of communication between patients and healthcare providers for managing chronic diseases. The objective of this study is to assess the capacity and willingness of patients to use information technology for managing chronic diseases.

Methods: A descriptive, cross-sectional study design was employed. Study was conducted in six tertiary care hospitals of Lahore, Pakistan. The study population consisted of patients aged ≥18 years and diagnosed with a minimum of one chronic non-communicable disease. A structured questionnaire was administered to the study participants for data collection. SPSS was used for data analysis.

Results: Among the 400 respondents, hypertension (39.5%) was the leading chronic condition followed by diabetes (27.5%). Majority of the patients owned a cell phone (90.7%) and had internet access (66.2%). Almost half of the respondents (51.0%) were willing to use text messages; whereas 78.5% and 75.7% of the respondents were reluctant to use video conference and e-mail as a source of communication with healthcare providers. Reason for unwillingness to use e-mail was the patients' desire to be directly examined by the doctor; whereas unfamiliarity with the use of text message and video conference was the major reason for not using these technologies. Logistic regression analysis revealed that interest in using e-mail to interact with specialist was more among those participants who had good self-reported health (OR = 2.579, 95%CI = 1.276-5.212, p = .008), access to internet (OR = 5.416, 95%CI = 2.777-10.564, p < .001), and those who owned a cell phone (OR = 12.944, 95%CI = 1.751-95.704, p = .012). Interest in using text messages to interact with specialist was more among participants with middle-income group (OR = 2.303, 95%CI = 1.389-3.818, p < .001), residency in close proximity to healthcare professional (OR = 3.529, 95%CI = 2.333-5.339, p < .001), access to internet (OR = 3.253, 95%CI = 2.102-5.033, p < .001) and among those who owned a cell phone (OR = 46.709, 95%CI = 6.335-344.377, p < .001). Interest in using video conference to interact with specialist was more among those participants who had access to internet (OR = 5.840, 95%CI = 2.825-12.069, p < .001) and among those who owned a cell phone (OR = 11.177, 95%CI = 1.510-82.725, p = .018).

Conclusion: This study concluded that nearly half of the respondents were willing to use text messages; whereas, majority was reluctant in using video conference and e-mail as a source of communication with healthcare providers. Most of the respondents who were located farther from the health care provider were willing to use video conferencing in case it could save more than 60 minutes of their time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209654PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328230PMC
September 2019

Nano-sized Droplets of Self-Emulsifying System for Enhancing Oral Bioavailability of Chemotherapeutic Agent VP-16 in Rats: A Nano Lipid Carrier for BCS Class IV Drugs.

J Pharm Pharm Sci 2018 ;21(1):398-408

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan.

Purpose: The purpose of this study was to investigate the ability of a self-nano-emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of a BCS class IV drug, etoposide (VP-16).

Method: A series of SNEDDS formulations with VP-16 were prepared consisting of medium chain triglycerides, polysorbate 80, diethylene glycol monoethyl ether and propylene glycol monolaurate type-1.  Based on an obtained ternary phase diagram, an optimum formulation was selected and characterized in terms of size, zeta potential, loading, morphology and in vitro drug release. The pharmacokinetic parameters and oral bioavailability of VP-16 suspension and VP-16 in SNEDDS was assessed using 30 Male Sprague-Dawley rats and compared with the commercial product (VePesid®).

Results: Pharmacokinetic data showed that the mean values for AUC0-t of VP-16 in SNEDDS was 6.4 fold higher compared to a drug suspension and 2.4-folds higher than VePesid®. Similarly, the mean value for Cmax of VP-16 in SNEDDS (1.13± 0.07 µg/ml µg.h/mL) was higher than VePesid® (0.62± 0.09 µg/mL) and drug suspension (0.13± 0.07 µg/mL).

Conclusion: The SNEDDS formulation was able to enhance the oral bioavailability of the BCS Class IV chemotherapeutic agent VP-16 by increasing the dissolution and absorption of the drug. A good in vitro in vivo correlation was found between the in vitro dissolution and in vivo absorption data of VP-16 SNEDDS preparation. Therefore, SNEDDS formulations might be a very promising approach for BCS Class IV drugs.
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http://dx.doi.org/10.18433/jpps30097DOI Listing
September 2019

Attitude, perception, willingness, motivation and barriers to practice-based research: A cross-sectional survey of hospital pharmacists in Lahore, Punjab, Pakistan.

PLoS One 2018 7;13(9):e0203568. Epub 2018 Sep 7.

Akhtar Saeed College of Pharmaceutical Sciences, Lahore, Pakistan.

Background And Objectives: Practice-based research (PBR) is of pivotal importance for hospital pharmacists which not only up-grades the profession but also improves the patient care. This study aimed to evaluate the attitude, perception, willingness, motivation and barriers to PBR among hospital pharmacists in Pakistan.

Methods: A descriptive, cross sectional study design was employed. Data were collected between 1st December, 2017 and 1st March, 2018 from 130 hospital pharmacists employed in 41 hospitals of Lahore, Pakistan. A survey instrument comprising of six sections was designed to determine the attitude, perception, willingness, motivation and barriers to PBR. Data were analyzed by using Statistical Package for Social Sciences (IBM SPSS Statistics for Windows, version 21.0, Armonk, NY: IBM Corp.). The normality of the data was determined through Shapiro-Wilks and Kolmogorov-Smirnov tests. Independent Samples Mann-Whitney U Test and Independent Samples Kruskal-Wallis Test were carried out to test if there were differences among the characteristics of the hospital pharmacists. Logistic regression analysis was used to figure out the factors associated with attitude, perceptions, willingness and motivation towards PBR. A p-value <0.05 was used for statistical significance of differences.

Results: A total of 141 pharmacists were approached. Among them, 130 responded to the survey (response rate 92%). Out of a maximum score i.e., 5 (100%) the respondents obtained a median score of 4 (IQR = 0) for attitude, perception and motivation towards PBR; whereas, a median score of 4 (IQR = 1) was obtained for willingness thus demonstrating fair positive attitude, good perceptions, increased motivation and willingness towards PBR. The most common barrier limiting the pharmacists' participation in PBR was lack of time (23.8%) followed by lack of incentives (16.2%) and lack of support (14.6%). Results of the logistic regression analysis revealed that hospital pharmacists practicing in the inpatient settings had 4.56 times more positive attitude towards PBR (OR = 4.56, 95%CI = 1.07─19.42, p-value = 0.040) as compared to those practicing in the outpatient settings. The male hospital pharmacists (OR = 8.86, 95%CI = 1.15-53.74, p-value = 0.017), those practicing in the outpatient (OR = 23.51, 95%CI = 2.04─271.53, p-value = 0.011) and inpatient settings had increased motivation towards PBR (OR = 12.24, 95%CI = 1.61─94.66, p-value = 0.016).

Conclusion: Despite the presence of several barriers, the respondents had fair positive attitude, good perceptions, increased motivation and willingness towards PBR which is a promising finding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203568PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128607PMC
February 2019

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

Pak J Pharm Sci 2018 Jan;31(1(Suppl.)):345-351

Dana Pharmaceuticals Factory, Nablus-West Bank, Palestinian Authority.

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.
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January 2018

Cross-linked guar gum and sodium borate based microspheres as colon-targeted anticancer drug delivery systems for 5-fluorouracil.

Pak J Pharm Sci 2017 Nov;30(6(Supplementary)):2329-2336

Nisar-ur-Rahman.

The aim was to prepare cross linked polymer of 5-fluorouracil loaded microspheres containing guar gum and sodium borate for colon-targeted drug delivery systems. Micro spheres were prepared using emulsification cross linking method. The influence of drug polymer ratio, cross linker agent concentrations and cross linking timing on in vitro drug release and characteristics in terms of drug loading, entrapment efficiency and yielding percentage were investigated. The optimum drug loading, entrapment efficiency and percent yield were obtained from formulations with the lowest content of cross linker agent over 2 h of cross linking timing but with the highest drug to polymer ratio 1:11. The optimum in vitro drug release was obvious upon decreasing drug to polymer ratio up to 1:09, resulting in 81.5% drug release over 24 h. In conclusion, micro spheres composed of gaur gum and sodium borate can delay and control the release of 5-fluorouracil over 24 h. Thus, further in vivo studies are suggested for final assessment.
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November 2017

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug.

J Pharm Pharm Sci 2017 ;20(0):305-318

College of Pharmacy, Al Ain University of Science and Technology, Al Ain, Abu Dhabi, UAE.

Purpose: Liposomes have been studied as a colloidal carrier in drug delivery systems, especially for oral administration. However, their low structural integrity in the gut is still a major shortcoming. Membrane disruptive effects of physiological bile salts in the small intestine result in premature drug release prior to intestinal absorption. Thus, we analyzed the stabilizing effect of sodium deoxycholate when incorporated into nano-sized liposomes.

Method: Cefotaxime-loaded liposomes were prepared with different sodium deoxycholate concentrations (3.75- 30 mM) by rotary film evaporation followed by nano-size reduction. The physical integrity of liposomes was evaluated by monitoring cefotaxime leakage, particle sizes in different simulated physiological media. The oral bioavailability and pharmacokinetics of cefotaxime was assessed in rats (n = 6 per group) after single dose of drug-encapsulated in liposomes containing bile salt, drug in conventional liposomes, and cefotaxime solution (oral and intravenous).

Results: Simulated gastric fluid with low pH showed less effect on the stability of liposomes in comparison to media containing physiological bile salts.  Liposomes containing 15 mM sodium deoxycholate were most stable in size and retained the majority of encapsulated cefotaxime even in fed state of simulated intestinal fluid being the most destructive media. Pharmacokinetics data showed an increase in Cmax and AUC0-inf in the following order: cefotaxime solution < conventional liposomes < liposomes made with bile salts. The total oral bioavailability of cefotaxime in liposomes containing bile salt was found to be 5-times higher compared to cefotaxime solution and twice as much as in conventional liposomes.

Conclusion: Incorporation of bile salts, initially used as membrane permeation enhancer, also acted as a stabilizer against physiological bile salts. The nano-sized liposomes containing sodium deoxycholate were able to reduce the leakage of encapsulated cefotaxime in the gut due to the improved vesicle stability and to enhance the oral bioavailability of acid-labile drugs up to 5-fold. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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http://dx.doi.org/10.18433/J3CK88DOI Listing
May 2018

Mixed Micelles Loaded with Bile Salt: An Approach to Enhance Intestinal Transport of the BCS Class III Drug Cefotaxime in Rats.

Eur J Drug Metab Pharmacokinet 2017 Aug;42(4):635-645

Department of Pharmacology and Toxicology, Faculty of Medicine, University of Novi Sad, 21000, Novi Sad, Serbia.

Background And Objectives: Cefotaxime is a class III drug according to the Biopharmaceutical Classification System due to low intestinal permeability based on poor oral bioavailability. Bile salt compounds have been shown to be effective additive for drug permeation through several biological membranes. The main purpose of this study was to investigate the ability of a mixed micelles made of phosphatidylcholine, sodium deoxycholate, and loaded with a cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex to enhance the oral bioavailability of cefotaxime in rats.

Methods: Thin-film hydration method was used to prepare cefotaxime-loaded mixed micelles using different bile salt concentrations (0.87-25 mM of sodium deoxycholate). Overall, micelle sizes ranging from 86.9 to 155.6 nm were produced with negative zeta potential values from -15.9 to -19.5 mV and drug loading from 10.5 to 18.9 %. The oral bioavailability of cefotaxime in mixed micellar formulation was assessed and the pharmacokinetic parameters were compared with cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex and cefotaxime aqueous solution. 24 Male Wistar rats were randomly allocated into four groups (n = 6, per group) to receive the following: (1) a single intravenous dose of cefotaxime (25 mg/kg) in sterilized normal saline solution for injection; (2) a single oral dose of mixed micelles (100 mg/kg of cefotaxime) in phosphate buffered saline administered by oral gavage; (3) a single oral dose of cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (100 mg/kg of cefotaxime) in phosphate buffered saline administered by oral gavage; (4) a single oral dose of free cefotaxime (100 mg/kg) in aqueous solution administered by oral gavage. Blood samples were collected for up to 24 h and cefotaxime analyzed using a validated HPLC assay.

Results: Pharmacokinetic data showed that the oral bioavailability of cefotaxime in mixed micelles was found to be 4.91 % higher compared to the cefotaxime in aqueous solution (1.30 %). Maximum concentration (C ) of cefotaxime in mixed micellar formulation was higher (1.08 ± 0.1 µg/ml) compared to the cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (0.69 ± 0.1 µg/ml) and cefotaxime in aqueous solution (0.52 ± 0.1 µg/ml). Similarly, the mean values for area under the plasma concentration-time curve extrapolated to infinity (AUC) of cefotaxime in the mixed micellar formulation was higher (3.89 ± 0.9 μg·h/mL) compared to the cefotaxime-3α,7α-dihydroxy-12-keto-5β-cholanate complex (1.52 ± 0.2 μg·h/mL) and cefotaxime in aqueous solution (1.03 ± 0.4 μg·h/mL), respectively.

Conclusion: The mixed micellar formulation was able to increase the oral bioavailability of the BCS Class III drug cefotaxime up to fourfold by enhancing drug permeation through the mucosal membrane of the small intestine.
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http://dx.doi.org/10.1007/s13318-016-0375-9DOI Listing
August 2017
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