Fatma Ahmed Ismail

Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing.

Mucoadhesive patches containing 10mg miconazole nitrate were evaluated. The patches were prepared with ionic polymers, sodium carboxymethyl cellulose (SCMC) and chitosan, or non-ionic polymers, polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC) and hydroxypropylmethyl cellulose (HPMC). Convenient bioadhesion, acceptable elasticity, swelling and surface pH were obtained. Patches exhibited sustained release over more than 5h and the addition of polyvinyl pyrrolidone (PVP) generally enhanced the release rate. Optimum release behaviour was shown with patches containing 10% w/v PVA and 5% w/v PVP. Study of the in vivo release from this formulation revealed uniform and effective salivary levels with adequate comfort and compliance during at least 6h. On the contrary, in vivo release of the commercial oral gel product resulted in a burst and transient release of miconazole, which diminished sharply after the first hour of application. Storage of these patches for 6 months did not affect the elastic properties, however, enhanced release rates were observed due to marked changes in the crystal habit of the drug.

Mucoadhesive Delivery Systems. I. Evaluation of Mucoadhesive Polymers for Buccal Tablet Formulation

Different types of mucoadhesive polymers, intended for buccal tablet formulation, were investigated for their comparative mucoadhesive force, swelling behavior, residence time and surface pH. The selected polymers were carbopols (CP934, and CP940), polycarbophil (PC), sodium carboxymethyl cellulose (SCMC) and pectin representing the anionic type, while chitosan (Ch) as cationic polymer and hydroxypropylmethyl cellulose (HPMC) as a non‐ionic polymer. Results revealed that polyacrylic acid derivatives (PAA) showed the highest bioadhesion force, prolonged residence time and high surface acidity. SCMC and chitosan ensured promising bioadhesive characteristics, whilst HPMC and pectin exhibited weaker bioadhesion. Different polymer combinations as well as formulations were evaluated to improve the mucoadhesive performance of the tablets. Bioadhesive tablet formulations containing either 5% CP934, 65% HPMC and 30% spray‐dried lactose or 2% PC, 68% HPMC and 30% mannitol showed optimum mucoadhesion and suitable residence time. SCMC, when formulated individually, exhibited promising bioadhesion, acceptable swelling, convenient residence time and surface pH. In‐vivo trials of these formulations proved non‐irritative and prolonged residence of the mucoadhesive tablets on human buccal mucosa for 8 to 13 h.

In Situ Gel Formulations for Gene Delivery: Release and Myotoxicity Studies

The in vitro release of plasmid DNA and salmon sperm DNA from in situ gel formulations was investigated. Two in situ gel systems were studied: (a) an interpolymeric complex (IPC) of water-soluble polymers polymethacrylic acid (PMA) and polyethylene glycol (PEG) and (b) a hydroxypropylmethylcellulose–carbopol system (H:C). Two-way analysis of variance with replication demonstrated that both gel composition and medium pH influenced significantly the release of plasmid DNA from in situ gel formulations. When the release of both types of DNA was compared, higher release was observed for plasmid DNA compared to genomic salmon sperm DNA. Conformational analysis of the released plasmid DNA showed that DNA was released without degradation, but with remarkable conversion from supercoiled (SC) to open circular (OC). In addition, the tested in situ gel systems demonstrated protection from DNAse I degradation. The myotoxicity of the injectable gelling solutions was assessed by the cumulative release of creatine kinase (CK) over 120 min from the isolated rodent extensor digitorum longus (EDL) muscle. A higher level of cumulative CK was observed for IPC when compared to H:C (2:1). These results demonstrate that the in situ gelling systems can be considered as a valuable injectable controlled-delivery system for pDNA in their role to provide protection from DNAse degradation.

Design and In Vitro Evaluation of Polymeric Formulae of Simvastatin for Local Bone Induction

ABSTRACT Simvastatin (SVS), a cholesterol-lowering drug, has been shown to stimulate bone formation. This study deals with the design and in vitro evaluation of local delivery systems for simvastatin. They are intended to treat bony defects resulting from periodontitis or to induce osteogenesis around the titanium implants. Granules and gels were formulated using bioerodible/biocompatible polymers, namely hydroxypropylmethyl cellulose (H), sodium carboxymethyl cellulose (C), and chitosan (Ch). The in vitro release profiles and kinetics were evaluated and the swelling and/or erosion was monitored. Differential scanning calorimetry (DSC) and infrared (IR) were used to detect any SVS/polymer interactions that may affect drug release. The results revealed variable extents of controlled drug release from the designed formulae depending on the polymer nature. About 50% cumulative SVS was released from both H granules and gel formulae within 24 h and ∼66% and ∼88% from C granules and gel, respectively. Ch formulae exhibited ∼50% release from granules and ∼30% from gel.

Preparation and evaluation of periodontal films based on polyelectrolyte complex formation.

Abstract Local intra-pocket drug delivery devices can provide an effective concentration of the antimicrobial agent at the site of action with avoidance of undesirable side effects. This study explored the application of chitosan-alginate and chitosan-pectin polyelectrolyte complex (PEC) films as drug release regulators for tetracycline HCl (Tc) to treat periodontal pockets. Periodontal films with 1:1 Tc:PEC ratio were prepared using 1:1 chitosan (Ch) to sodium alginate (A) or 1:3 Ch to pectin (P). The scanning electron microscope showed acceptable film appearance and differential scanning calorimetry analysis confirmed complex formation. The in vitro release studies for both films showed a burst drug release, followed by prolonged release for 70 h. A prolonged antibacterial activity of both films against Staphylococcus aureus ATCC 6538 was observed over a period of 21 days. Aging studies indicated that the five months storage period in freezer did not significantly influence the drug release profile or the antibacterial activity of both films. Clinical evaluation showed a significant reduction in pocket depth (p < 0.0001) to their normal values (≤3 mm). PEC films could be exploited as a prolonged drug release devices for treatment of periodontal pockets.

Adsorption of ketoprofen and bumadizone calcium on aluminium-containing antacids and its effect on ketoprofen bioavailability in man

Abstract The present study reports the adsorption of ketoprofen and bumadizone calcium, two non-steroidal anti-inflammatory drugs, on three aluminium-containing antacids. The type of aluminium antacid, the initial drug concentration and the pH of the medium were found to influence drug adsorption. At pH 3–4, binding of both drugs to aluminium hydroxide and dihydroxyaluminium sodium carbonate indicated co-operative adsorption, while adsorption profiles of bumadizone calcium on aluminium glycinate suggested a constant partitioning pattern. pH (1–8) adsorption profiles for ketoprofen and bumadizone calcium binding to aluminium hydroxide and dihydroxyaluminium sodium carbonate passed through a maximum in the pH range 3.5–4.5. Antacid dissolution during the adsorption runs was also investigated at different pH values. The effect of coadministration of ketoprofen and aluminium hydroxide on the bioavailability of ketoprofen was investigated in healthy volunteers. Urine was collected for 24 h following drug administration and samples were analyzed by HPLC for ketoprofen and its conjugates. The urinary excretion data indicated a decrease in drug bioavailability upon coadministration with aluminium hydroxide.

Bioavailability of Eight Brands of Ampicillin Capsules

AbstractAn in vivo absorption study was performed in a crossover fashion on 6 healthy volunteers (4 males and 2 females) to compare the bioavailability of 8 brands of ampicillin capsules. Absorption was assessed by a urinary excretion method in which the drug was assayed chemically. Statistical analysis of the results was carried out to evaluate the significance of differences between brands and between subjects. Results of the analysis of variance indicated no significant differences between the tested brands of ampicillin capsules. However, significant differences between brand A and brand B were found on using the student t-test. A significant intersubject variation was also found between the volunteers participated in the present study.

Effect of metoclopramide on ketoprofen pharmacokinetics in man

Abstract The effect of oral administration of metoclopramide (10 mg) on the absorption of ketoprofen from a capsule dosage form (50 mg) was studied in four healthy subjects in a cross-over design. The plasma concentrations of ketoprofen were determined by a HPLC technique. The results demonstrated a marked decrease in drug levels during coadministration with metoclopramide in the first 2 h post-dose. Metoclopramide resulted in markedly lower AUC and C max values with a longer T max of ketoprofen in comparison with the corresponding values for the drug alone. The results suggest that the gastric phase of ketoprofen absorption is the determinant step of the process. Rapid transit of the capsule, due to metoclopramide, reduces the time required for adequate dissolution and absorption.

Disease and Drug-Induced Changes in Naproxen Binding to Plasma

AbstractPlasma binding data were generated for the nonsteroidal antiinflammatory drug, napproxen, by equilibrium dialysis. Plasma samples were obtained from 7 healthy volunteers, from 43 uremic patients and from a blood bank. Drug in plasma was equilibrated with buffer across a suitable membrane. Buffer and plasma compartments were analysed by HPLC for free and total naproxen concentrations. Creatinine, urea and albumin plasma levels were determined by suitable methods. Binding of naproxen to healthy plasma exceeded 99% at concentrations attained in therapy. Free naproxen fraction was consistantly higher in uremic plasma with binding values ranging from 89-99%. The correlations examined indicated a dependence of naproxen free fraction on the degree of renal impairment, indicated by creatinine and urea plasma levels. Binding of naproxen was independent of albumin concentration at plasma albumin levels higher than 15 g/1. Apart from disease, plasma binding of naproxen was also perturbed, but to a lesser deg...

A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: Preparation, characterization and in vivo evaluation

ABSTRACT This work aimed at designing efficient safe delivery system for intranasal (IN) brain targeting of the water soluble anti‐ migraine drug Almotriptan malate (ALM). Solid lipid nanoparticles (SLNs) were prepared by w/o/w double emulsion‐solvent evaporation method. Selection of the optimized SLNs formula was based on evaluating particle size (PS), poly dispersity index (PDI) and entrapment efficiency (%EE). Optimized formula exhibited acceptable ranges; PS of 207.9nm, PDI of 0.41 and %EE of 50.81%. Poloxamer 407 (Plx) at different concentrations (16%, 18%, 20% w/v), with different mucoadhesive polymers (Carbopol‐974P, Na alginate, Na‐CMC) were evaluated for gelling time and temperature, pH and mucoadhesion. The chosen mucoadhesive in‐situ gel formula; 18% Plx 407 based‐0.75%w/v Na‐CMC, showed acceptable results, so that the optimized SLNs formula was further dispersed in it and evaluated for in vitro release, stability, in vivo and pharmacokinetics studies. Biomarkers’ evaluation and histopathological examination were also investigated. Results revealed rapid ALM brain delivery of the optimized formula; Brain/blood ratios at 10min. for NF (SLNs based IN in‐situ gel), ND (Free ALM IN in situ gel) and ALM i.v. (ALM IV solution) were 0.89, 0.19 and 0.31, respectively. Toxicological results confirmed the safety of NF for nasal administration. The achieved out comings are encouraging for further clinical trials of the developed system in humans in future research.