Publications by authors named "Mohammed F Aldawsari"

16 Publications

  • Page 1 of 1

Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188.

Pharmaceuticals (Basel) 2021 Apr 26;14(5). Epub 2021 Apr 26.

Department of Pharmaceutics and Central Lab, College of Pharmacy, King Saud University, Riyadh P.O. Box 2457, Saudi Arabia.

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.
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http://dx.doi.org/10.3390/ph14050411DOI Listing
April 2021

Enhanced Cytotoxic Activity of Docetaxel-Loaded Silk Fibroin Nanoparticles against Breast Cancer Cells.

Polymers (Basel) 2021 Apr 27;13(9). Epub 2021 Apr 27.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.
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http://dx.doi.org/10.3390/polym13091416DOI Listing
April 2021

Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity.

Nanomaterials (Basel) 2021 Mar 22;11(3). Epub 2021 Mar 22.

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of , which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV-VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.
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http://dx.doi.org/10.3390/nano11030808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004202PMC
March 2021

Development of spray-dried amorphous solid dispersions of tadalafil using glycyrrhizin for enhanced dissolution and aphrodisiac activity in male rats.

Saudi Pharm J 2020 Dec 21;28(12):1817-1826. Epub 2020 Nov 21.

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds' increase in dissolution rate compared to pure TDL. The results obtained from the  study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature.
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http://dx.doi.org/10.1016/j.jsps.2020.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783211PMC
December 2020

Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach.

Pharmaceuticals (Basel) 2020 Dec 17;13(12). Epub 2020 Dec 17.

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.

Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this research, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting the moisture-activated dry granulation (MADG) process. In this method, heating and drying steps were omitted so, called green granulation process. A 3 full-factorial design was performed for optimization of key process variables, namely the granulation fluid level (X) and the wet massing time (X). Granulation of CNG was carried out in the presence of polyvinylpyrrolidone, and the prepared granules were compressed into tablets. Regression analysis demonstrated the significant ( ≤ 0.05) effect of X and X on properties of granules and corresponding tablets, with pronounced impact of X. Additionally, marked improvement of granules' properties and tableting of CNG were observed. Furthermore, the optimized process conditions that produced good flow properties of granules and acceptable tablets were high level of granulation fluid (3.41% /) and short wet massing time (1.0 min). Finally, the MADG process gives the opportunity to ameliorate the poor flow and tableting problems of CNG with lower amounts of excipients, which are important for successful development of uniform dosage unit.
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http://dx.doi.org/10.3390/ph13120473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765871PMC
December 2020

Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization.

Pharmaceuticals (Basel) 2020 Dec 5;13(12). Epub 2020 Dec 5.

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.

Sulpiride (SUL) is a dopamine D-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A 3 full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X) and Prosolv (X) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58 ± 0.52 KP, friability of 0.73 ± 0.158%, disintegration time of 37.5 ± 1.87 s and drug release of 100.51 ± 1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant ( < 0.01) increase in C and AUC() and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action.
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http://dx.doi.org/10.3390/ph13120446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762047PMC
December 2020

Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells.

AAPS PharmSciTech 2020 Nov 4;21(8):304. Epub 2020 Nov 4.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, USA.

Hispolon is a small molecular weight polyphenol that has antioxidant, anti-inflammatory, and anti-proliferative activities. Our recent study has demonstrated hispolon as a potent apoptosis inducer in melanoma cell lines. Doxorubicin is a broad spectrum first-line treatment for various kinds of cancers. In this study, co-delivery of doxorubicin and hispolon using a liposomal system in B16BL6 melanoma cell lines for synergistic cytotoxic effects was investigated. Liposomes were prepared using a lipid film hydration method and loaded with doxorubicin or hispolon. The formulations were characterized for particle size distribution, release profile, and encapsulation efficiency (EE). In addition, in vitro cytotoxicity, in vitro cell apoptosis, and cellular uptake were evaluated. Liposomes exhibited small particle size (mean diameter ~ 100 nm) and narrow size distribution (polydispersity index (< 0.2) and high drug EE% (> 90%). The release from liposomes showed slower release compared to free drug solution as an additional time required for the release of drug from the liposome lipid bilayer. Liposome loaded with doxorubicin or hispolon exhibited significantly higher cytotoxicity against B16BL6 melanoma cells as compared to doxorubicin solution or hispolon solution. Likewise, co-delivery of hispolon and doxorubicin liposomes showed two-fold and three-fold higher cytotoxicity, as compared to hispolon liposomes or doxorubicin liposomes, respectively. In addition, co-delivery of doxorubicin and hispolon in liposomes enhanced apoptosis more than the individual drugs in the liposome formulation. In conclusion, the co-delivery of hispolon and doxorubicin could be a promising therapeutic approach to improve clinical outcomes against melanoma.
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http://dx.doi.org/10.1208/s12249-020-01846-2DOI Listing
November 2020

Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human carcinoma A549 lung cell lines.

Chem Phys Lipids 2020 Nov 20;233:105003. Epub 2020 Oct 20.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 3 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176-787 nm), fairly monodisperse (PDI indices 0.19-0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31-87.87 %) (3.35-31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.
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http://dx.doi.org/10.1016/j.chemphyslip.2020.105003DOI Listing
November 2020

Eluxadoline Loaded Solid Lipid Nanoparticles for Improved Colon Targeting in Rat Model of Ulcerative Colitis.

Pharmaceuticals (Basel) 2020 Sep 19;13(9). Epub 2020 Sep 19.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid 21110, Jordan.

The aim of the current study was to evaluate the therapeutics potential of eluxadoline (ELX) loaded solid lipid nanoparticles (SLNs) in ulcerative colitis. ELX loaded SLNs were prepared using three different lipids according to the solvent emulsification technique. The optimization of prepared SLNs (F1-F3) were carried out based on size, PDI, zeta potential, percent drug entrapment (%EE), and loading (%DL). The lipid (stearic acid) based SLNs (F2) was optimized with particle size (266.0 ± 6.4 nm), PDI (0.217 ± 0.04), zeta potential (31.2 ± 5.19 mV), EE (65.0 ± 4.8%), and DL (4.60 ± 0.8%). The optimized SLNs (F2) was further evaluated by DSC, FTIR, SEM, in vitro release, and stability studies, which confirmed the successful encapsulation of ELX in SLNs. The efficacy of optimized SLNs (F2) in comparison to the pure ELX drug was assessed in acetic acid induced colitis rat models. It was observed that the delivery of ELX by SLNs alleviated the induced acetic acid colitis significantly. Thus, ELX loaded SLNs delivery to the colon has a significant potential to be developed for the treatment of ulcerative colitis.
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http://dx.doi.org/10.3390/ph13090255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559404PMC
September 2020

The Interaction of the Microtubule Targeting Anticancer Drug Colchicine with Human Glutathione Transferases.

Curr Pharm Des 2020 ;26(40):5205-5212

Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos Street, GR-11855-Athens, Greece.

Background: Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that have been shown to be involved in the development of multi-drug resistance (MDR) mechanism toward chemotherapeutic agents. GST inhibitors have, therefore, emerged as promising chemosensitizers to manage and reverse MDR. Colchicine (COL) is a classical antimitotic, tubulin-binding agent (TBA) which is being explored as anticancer drug.

Methods: In the present work, the interaction of COL and its derivative 2,3-didemethylcolchicine (2,3-DDCOL) with human glutathione transferases (hGSTA1-1, hGSTP1-1, hGSTM1-1) was investigated by inhibition analysis, molecular modelling and molecular dynamics simulations.

Results: The results showed that both compounds bind reversibly to human GSTs and behave as potent inhibitors. hGSTA1-1 was the most sensitive enzyme to inhibition by COL with IC50 22 μΜ. Molecular modelling predicted that COL overlaps with both the hydrophobic (H-site) and glutathione binding site (G-site) and polar interactions appear to be the driving force for its positioning and recognition at the binding site. The interaction of COL with other members of GST family (hGSTA2-2, hGSTM3-3, hGSTM3-2) was also investigated with similar results.

Conclusion: The results of the present study might be useful in future drug design and development efforts towards human GSTs.
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http://dx.doi.org/10.2174/1381612826666200724154711DOI Listing
April 2021

Design, Optimization, and Correlation of In Vitro/In Vivo Disintegration of Novel Fast Orally Disintegrating Tablet of High Dose Metformin Hydrochloride Using Moisture Activated Dry Granulation Process and Quality by Design Approach.

Pharmaceutics 2020 Jun 27;12(7). Epub 2020 Jun 27.

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.

Compression of cohesive, poorly compactable, and high-dose metformin hydrochloride into the orally disintegrating tablet (ODT) is challenging. The objective of this study was to develop metformin ODT using the moisture activated dry granulation (MADG) process. There are no reports in the literature regarding the development of ODT based on MADG technology. The feasibility of developing metformin ODT was assessed utilizing a 3 full factorial design to elucidate the influence of water amount (X) and the amount of pregelatinized starch (PGS; X) as independent variables on key granules and tablets' characteristics. The prepared granules and tablets were characterized for granule size, bulk density, flow properties, tablets' weight variation, breaking force, friability, capping tendency, in vitro and in vivo disintegration, and drug release. Regression analysis showed that X and X had a significant ( ≤ 0.05) impact on key granules and tablets' properties with a predominant effect of the water amount. Otherwise, the amount of PGS had a pronounced effect on tablet disintegration. Optimized ODT was found to show better mechanical strength, low friability, and short disintegration time in the oral cavity. Finally, this technique is expected to provide better ODT for many kinds of high-dose drugs that can improve the quality of life of patients.
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http://dx.doi.org/10.3390/pharmaceutics12070598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408287PMC
June 2020

Development of Enzybiotics: The Ph28 Gene of Phage PH15 Is a Two-Domain Endolysin.

Antibiotics (Basel) 2020 Mar 30;9(4). Epub 2020 Mar 30.

Laboratory of Enzyme Technology, Department of Biotechnology, School of Food, Biotechnology and Development, Agricultural University of Athens, 75 Iera Odos Street, 11855 Athens, Greece.

Given the worldwide increase in antibiotic resistant bacteria, bacteriophage derived endolysins represent a very promising new alternative class of antibacterials in the fight against infectious diseases. Endolysins are able to degrade the prokaryotic cell wall, and therefore have potential to be exploited for biotechnological and medical purposes. is a Gram-positive multidrug-resistant (MDR) bacterium of human skin. It is a health concern as it is involved in nosocomial infections. Genome-based screening approach of the complete genome of virus PH15 allowed the identification of an endolysin gene (Ph28; NCBI accession number: YP_950690). Bioinformatics analysis of the Ph28 protein predicted that it is a two-domain enzyme composed by a CHAP (22-112) and MurNAc-LAA (171-349) domain. Phylogenetic analysis and molecular modelling studies revealed the structural and evolutionary features of both domains. The MurNAc-LAA domain was cloned, and expressed in BL21 (DE3). In turbidity reduction assays, the recombinant enzyme can lyse more efficiently untreated cells, compared to other strains, suggesting enhanced specificity for . These results suggest that the MurNAc-LAA domain from Ph28 endolysin may represent a promising new enzybiotic.
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http://dx.doi.org/10.3390/antibiotics9040148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235722PMC
March 2020

Development of Lipomer Nanoparticles for the Enhancement of Release, Anti-microbial Activity and Bioavailability of Delafloxacin.

Pharmaceutics 2020 Mar 11;12(3). Epub 2020 Mar 11.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Delafloxacin (DFL) is a novel potent and broad-spectrum fluoroquinolone group of antibiotics effective against both Gram-positive and negative aerobic and anaerobic bacteria In this study, DFL-loaded stearic acid (lipid) chitosan (polymer) hybrid nanoparticles (L-P-NPs) have been developed by single-emulsion-solvent evaporation technique. The mean particle size and polydispersity index (PDI) of optimized DFL-loaded L-P-NPs (F1-F3) were measured in the range of 299-368 nm and 0.215-0.269, respectively. The drug encapsulation efficiency (EE%) and loading capacity (LC%) of DFL-loaded L-P-NPs (F1-F3) were measured in the range of 64.9-80.4% and 1.7-3.8%, respectively. A sustained release of DFL was observed from optimized DFL-loaded L-P-NPs (F3). Minimum inhibitory concentration (MIC) values of the DFL-loaded L-P-NPs (F3) appeared typically to be four-fold lower than those of delafloxacin in the case of Gram-positive strains and was 2-4-fold more potent than those of delafloxacin against Gram-negative strains. The pharmacokinetic study in rats confirmed that the bioavailability (both rate and extent of absorption) of DFL-loaded L-P-NPs was significantly higher (2.3-fold) than the delafloxacin normal suspension. These results concluded that the newly optimized DFL-loaded L-P-NPs were more potent against both Gram-positive and negative strains of bacteria and highly bioavailable in comparison to delafloxacin normal suspension.
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http://dx.doi.org/10.3390/pharmaceutics12030252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151119PMC
March 2020

Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect.

J Thromb Thrombolysis 2020 Apr;49(3):404-412

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia.

The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles (RXB-PLGA-NPs) were prepared by emulsion solvent evaporation method and optimized using central composite design (CDD). The optimized RXB-PLGA-NPs (F8) with composition, PLGA (125 mg), PVA (0.5%w/w) and RXB (20 mg) was found optimum with particle size (496 ± 8.5 nm), PDI (0.607), ZP (- 18.41 ± 3.14 mV), %EE (87.9 ± 8.6) and %DL (9.5 ± 1.6). The optimized NPs (F8) was further evaluated in vitro for DSC, FTIR, SEM and in vitro release studies. A comparative pharmacokinetic studies with commercial tablet (XARELTO®) were conducted on fasted and fed state rats. Compared to commercial tablet (XARELTO®), the RXB-PLGA-NPs (F8) exhibited a significant enhancement of bioavailability in both fasted and fed state. In addition, the bioavailability of RXB from NPs (F8) was found unaffected in the presence of food.
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http://dx.doi.org/10.1007/s11239-019-02022-5DOI Listing
April 2020

Estimating the Solubility, Solution Thermodynamics, and Molecular Interaction of Aliskiren Hemifumarate in Alkylimidazolium Based Ionic Liquids.

Molecules 2019 Aug 1;24(15). Epub 2019 Aug 1.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Estimating the solubility and solution thermodynamics parameters of aliskiren hemifumarate (AHF) in three different room temperature ionic liquids (RTILs), Transcutol-HP (THP) and water are interesting as there is no solubility data available in the literature. In the current study, the solubility and solution thermodynamics of AHF in three different RTILs, THP and water at the temperature range from 298.2 to 318.2 K under air pressure 0.1 MP were evaluated. The solid phase evaluation by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) indicated no conversion of AHF into polymorph. The mole fraction solubility of AHF was found to be highest in 1-hexyl-3-methylimidazolium hexafluorophosphate (HMMHFP) ionic liquid (7.46 × 10) at 318.2 K. The obtained solubility values of AHF was regressed by the Apelblat and van't Hoff models with overall root mean square deviations () of 0.62% and 1.42%, respectively. The ideal solubility of AHF was higher compared to experimental solubility values at different temperatures. The lowest activity coefficient was found in HMMHFP, which confirmed highest molecular interaction between AHF-HMMHFP. The estimated thermodynamic parameters confirmed endothermic and entropy driven dissolution of AHF in different RTILs, THP, and water.
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http://dx.doi.org/10.3390/molecules24152807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695967PMC
August 2019

Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs.

Am J Vet Res 2018 Jan;79(1):73-82

OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. PROCEDURES In phase 1 of a 2-phase study, 2 gel formulations were developed that contained 1% midazolam in a poloxamer 407 (P1) or hydroxypropyl methylcellulose (H1) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2% midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase 1 results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase 1. RESULTS The H1 and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the P1 formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs.
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http://dx.doi.org/10.2460/ajvr.79.1.73DOI Listing
January 2018