Nawal M. Khalafallah

Propylene Glycol Liposomes as a Topical Delivery System for Miconazole Nitrate: Comparison with Conventional Liposomes

Propylene glycol (PG)-phospholipid vesicles have been advocated as flexible lipid vesicles for enhanced skin delivery of drugs. To further characterize the performance of these vesicles and to address some relevant pharmaceutical issues, miconazole nitrate(MN)-loaded PG nanoliposomes were prepared and characterized for vesicle size, entrapment efficiency, in vitro release, and vesicle stability. An issue of pharmaceutical importance is the time-dependent, dilution-driven diffusion of propylene glycol out of the vesicles. This was addressed by assessing propylene glycol using gas chromatography in the separated vesicles and monitoring its buildup in the medium after repeated dispersion of separated vesicles in fresh medium. Further, the antifungal activity of liposomal formulations under study was assessed using Candida albicans, and their in vitro skin permeation and retention were studied using human skin. At all instances, blank and drug-loaded conventional liposomes were included for comparison. The results provided evidence of controlled MN delivery, constant percent PG uptake in the vesicles (≈45.5%) in the PG concentration range 2.5 to 10%, improved vesicle stability, and enhanced skin deposition of MN with minimum skin permeation. These are key issues for different formulation and performance aspects of propylene glycol-phospholipid vesicles.

PG‐liposomes: novel lipid vesicles for skin delivery of drugs

A novel type of lipid vesicles, propylene glycol‐embodying liposomes or PG‐liposomes, composed of phospholipid, propylene glycol and water, is introduced. The new lipid vesicles were developed and investigated as carriers for skin delivery of the model drug, cinchocaine base. PG‐liposomes showed high entrapment efficiency and were stable for at least one month of storage at 5 ± 1 °C. Preliminary in‐vivo skin deposition studies, carried out using albino rabbit dorsal skin, showed that PG‐liposomes were superior to traditional liposomes, deformable liposomes and ethosomes, suggesting that PG‐liposomes, introduced in the current work, are promising carriers for skin delivery of drugs.

Alendronate PLGA microspheres with high loading efficiency for dental applications

Purpose: Alendronate sodium, used systemically as a bone protective agent, proved to also be effective locally in various dental bone applications. Development of alendronate-loaded microspheres with high loading efficiency for such applications would be greatly challenged by the hydrophilicity and low MW of the drug. The aim of this study was to incorporate alendronate sodium, into poly (lactide-co-glycolide) (PLGA) microspheres (MS) with high loading efficiency. Methods: Three multiple emulsion methods: water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O1/O2) and solid-in-oil-in-oil (S/O1/O2) were tested. In addition to entrapment efficiency, MS were characterized for surface morphology, particle size, in vitro drug release and in vitro degradation of the polymer matrix. Alendronate microspheres with maximum drug loading and good overall in vitro performance were obtained using the W/O1/O2 emulsion technique. Results: Drug release from the microspheres exhibited a triphasic release pattern over a period of 13 days, the last fast release phase being associated with more rapid degradation of the PLGA matrix. Conclusions: Biocompatible, biodegradable PLGA microspheres incorporating alendronate sodium with high loading efficiency obtained in this study may offer promise as a delivery system for bisphosphonates in dental and probably other clinical applications.

Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins.

This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins.

Development of Naftifine Hydrochloride Alcohol-Free Niosome Gel

Marketed topical gels of the antifungal drug naftifine hydrochloride contain 50% alcohol as cosolvent. Repeated exposure to alcohol could be detrimental to skin. The aim of this study is to develop an alcohol-free niosome gel containing 1% naftifine hydrochloride. Niosomes were prepared and formulation variables were optimized to achieve maximum entrapment coupled with stability. Maximum drug entrapment and niosome stability entailed imparting a negative charge to the vesicles where entrapment efficiency reached 50%. Niosomes were incorporated into a hydroxyethylcellulose gel. The final gel contained a total drug concentration of 1% (wt/wt) half of which was entrapped in the niosomes. The results suggest the potential usefulness of the niosome gel.

Vancomycin-Eluting Niosomes: A New Approach to the Inhibition of Staphylococcal Biofilm on Abiotic Surfaces

A new vancomycin (VCM)-eluting mixed bilayer niosome formulation was evaluated for the control of staphylococcal colonization and biofilm formation on abiotic surfaces, a niosome application not explored to date. Cosurfactant niosomes were prepared using a Span 60/Tween 40/cholesterol blend (1: 1: 2). Tween 40, a polyethoxylated amphiphile, was included to enhance VCM entrapment and confer niosomal surface properties precluding bacterial adhesion. VCM-eluting niosomes showed good quality attributes including relatively high entrapment efficiency (∼50%), association of Tween 40 with vesicles in a constant proportion (∼87%), biphasic release profile suitable for inhibiting early bacterial colonization, and long-term stability at 4°C for a 12-month study period. Niosomes significantly enhanced VCM activity against planktonic bacteria of nine staphylococcal strains. Using microtiter plates as abiotic surface, VCM-eluting niosomes proved superior to VCM in inhibiting biofilm formation, eradicating surface-borne biofilms, inhibiting biofilm growth, and interfering with biofilm induction by VCM subminimal inhibitory concentrations. Data suggest dual functionality of cosurfactant VCM-eluting niosomes as passive colonization inhibiting barrier and active antimicrobial-controlled delivery system, two functions recognized in infection control of abiotic surfaces and medical devices.

Bioavailability in Man of Nalidixic Acid Tablets

AbstractAn invivo absorption study was carried out in volunteers to compare the bioavailability of two brands of nalidixic acid tablets against a marketed paediatric suspension serving as a reference standard. Absorption was assessed by a urinary excretion method in which drug and major metabolite were assayed fluorimetrically. The excretion data were statistically treated. Results of the analysis of variance indicated a significant difference in rate, but not in extent of absorption, among the preparations tested. Poor disintegration quality of one of the tablet brands was found responsible for its delayed dissolution and, consequently, slow absorption.

Effect of active infection on cytochrome P450-mediated metabolism of cyclosporine in renal transplant patients.

Infections downregulate cytochrome‐P activities and thus may alter drug disposition, especially for drugs with a narrow therapeutic index. Cyclosporine (CyA), still used for the prevention of allograft rejection in renal transplant recipients in Egypt, seems to be affected by these infectious changes, based on random clinical observations. In the present study, the effects of bacterial and fungal infection on CyA metabolism were studied in renal transplant patients and subsequent nephrotoxicity was monitored.

Comparative Bioavailability of Norfloxacin Tablets Based on Blood and Urine Data

Objective: To assess the bioavailability of norfloxacin from urinary excretion relative to plasma concentration. Materials and Methods: Twelve healthy volunteers (22–33 years) participated in the study. Each received a previously developed (M), a local (L) and a multinational (Noroxin®) tablet (Ref), 400 mg each, according to a random balanced three-way crossover design on 3 different days. Blood samples were collected over a 12-hour period and urine over a 24-hour period. Norfloxacin concentrations were analyzed by a validated HPLC method. Results: An initial estimate of bioequivalence of the three products was obtained using analysis of variance on transformed data and based on confidence interval calculation. Elimination pharmacokinetic parameters (half-life and renal clearance) calculated from plasma concentration and urinary excretion data (mean values, n = 36) were comparable to reported values for norfloxacin. Interproduct differences in elimination parameters (mean values, n = 12) were statistically insignificant (F values, ANOVA). Strong association was found between the mean of plasma concentration and urinary excretion rates for many volunteers (F values, regression analysis). Relative bioavailability values calculated for the local and previously developed products relative to Noroxin were higher than 85% based on area under the curve and urinary excretion. Bioequivalence could not be established among the three tested products based on calculated 90% confidence intervals. Conclusion: Urinary excretion of norfloxacin may be a useful noninvasive tool for bioavailability assessment of norfloxacin oral formulations.

Entrapment efficiency of pyridoxine hydrochloride in unilamellar liposomes: experimental versus model-generated data.

Abstract The present study investigates the effect of the preparation method (four methods) and formulation additives (propylene glycol (PG) and cholesterol (CH)) on the entrapment efficiency (EE) of pyridoxine hydrochloride (vitamin B6 (VB6)), representing hydrophilic water-soluble low permeable vitamins, in unilamellar liposomes. The main aim is to compare determined EE with predicted values generated using a web-published, computational model. Results showed that among the different preparation methods, modified film hydration showed significantly higher EE (p < 0.05). With regard to formulation additives, PG (5% w/v) produced smaller vesicles size with narrow size distribution. Agreement between determined and model-generated EE values was more evident in formulae with narrow size distribution (polydispersity index (PdI) below 0.23). Formulae containing PG showed slightly higher determined than predicted EE values indicating vitamin–phospholipid bilayer interaction. Meanwhile, agreement between determined and predicted EE was limited to VB6-to-phospholipid ratio below (1.2:2). The comparison provided further insight into the usefulness of the prediction model factors affecting agreement between determined and predicted EE data.