Lobna M. Mortada

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.

Stability and Dissolution Rates of Corticosteroids in Polyethylene Glycol Solid Dispersions

AbstractA study has been made to examine the stability and dissolution rates of prednisolone, prednisone and hydrocortisone formulated as solid dispersions in polyethylene glycols. Of the five PEG samples used, three enhanced the chemical instability of the steroids; the effect being dependent on the PEG sample and storage conditions of the solid dispersions. Dissolution rates of the steroids were relatively fast from the solid dispersions and showed no significant changes upon storage. Using two methods of analysis (direct UV spectrophotometry and the USP blue tetrazolium method), it is concluded that the chemical instability of the steroids in some PEG samples was due to alterations in the dihydroxy acetone side chain. One of the decomposition products found appeared to be an acidic compound resulting from oxidation of the C17 side chain. The oxidation is presumably accelerated by a peroxide impurity in PEG samples.

The uptake of ampicillin and amoxycillin by some adsorbents

Abstract The in vitro uptake of ampicillin and amoxycillin by attapulgite, magnesium trisilicate, veegum and 3 types of kaolin has been studied. Adsorption data were obtained under conditions simulating in vivo with respect to changes in pH values, and the presence of electrolytes, a viscosity-imparting agent and a surfactant. Under all the conditions examined, amoxycillin was much less adsorbed than ampicillin. Desorption experiments at 37°C and pH values 2.0 and 6.5 showed only partial release of the adsorbed antibiotics; the maximum percentage was about 37 after 4 h. The presence of either veegum (l g) or kaolin (4 g) in the dissolution medium (900 ml) did not significantly alter the level of ampicillin or amoxycillin in solution during dissolution testing of the capsule. The data obtained emphasize the importance of investigating in vitro adsorption of drugs under conditions simulating in vivo.

Potential Improvement in the Shelf Life of Parenterals Using the Prodrug Approach: Bacampicillin and Talampicillin Hydrolysis Kinetics and Utilization Time

The utilization time for a parenteral prodrug solution with a bioavailable fraction of unity was defined as the time during which the total of the prodrug concentration and the drug concentration equals or exceeds 90% of the initial prodrug concentration. This utilization time was calculated as a function of pH, buffer, and temperature using the experimentally determined rate expressions for bacampicillin and talampicillin. The results were compared to the shelf life of ampicillin solutions under identical storage conditions. First-order rate constants were determined for conversion of the prodrugs to ampicillin (kc), for β-lactam degradation of the prodrugs (knc), for the overall loss of prodrugs (ksum), and for β-lactam degradation of ampicillin (kh) in aqueous solutions at 25.0 to 60.0°C, µ = 0.5, in the pH range 0.90 to 8.4. Loss of bacampicillin proceeded primarily by degradation at pH levels below 4 but was due predominantly to conversion at pH levels above 5. Loss of talampicillin was due primarily to conversion throughout the entire pH range. While the prodrug utilization times were approximately twice the shelf life of ampicillin in acidic solutions, ampicillin was significantly better in neutral solutions. The results illustrate the potential for increased prodrug storage periods when utilization time is defined on the basis of the bioactivity rather than on the prodrug concentration alone.

The In-Vitro Uptake of a Low Dose Drug (Riboflavine) by Some Adsorbents

AbstractAn investigation was carried out of the in-vitro adsorption of a low-dose model drug (riboflavine) by three typzs of kaolin, attapulgite, magnesium trisilicate and a grade of magnesium aluminium silicate (veegumR. The adsorption experiments were designed under conditions simulating in-vivo with respect to variations in pH values, volume of the adsorption medium, and the presence of electrolytes, a hydrophilic colloid and a surfactant. Under all conditions examined, riboflavine adsorption followed the sequence veegum attapulgite kaolin magnesium trisilicateThe presence of either veegumR (1 g) or kaolin (4 g) in the medium reduced the level of drug in solution during dissolution rate testing of capsules. Desorption results suggest only partial release of the adsorbed drug. The results obtained emphasiz,e the strong uptake of a potent ionic drug by the various silicates commonly used in pharmacy.

Correlation of Urinary Excretion with in Vitro Dissolution Using Four Dissolution Methods for Aiipicillin Capsules

AbstractThe in vitro release of ampicillin from 8 brands of ampicillin capsules, using four dissolution apparatus, was determined. These apparatus were the USP dissolution apparatus, the USP paddle stirrer apparatus, the USP disintegration apparatus and the spiral—stirrer apparatus. Significance of the differences in dissolution between brands and between methods were tested. Analysis of variance of the dissolution data showed statistically significant differences between brands and between methods at selected time. The paddle method showed superior discriminating capacity than the other methods. Correlation between the present in vitro data and the previously reported in vivo data, in order to find the apparatus capable to mimic in vivo release of ampicillin from capsules, was also determined.

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 Attapulgite on the Bioavailability of a Model Low Dose Drug (Riboflavine) in Humans

AbstractIn human volunteers, both the rate and extent of urinary excretion of riboflavine were significantly reduced (p<0.05) when attapulgite was co-administered with the drug. About 50% reduction occurred in the cumulative amount excreted following the concurrent administration of 10 mg riboflavine in solution form and 2 g of regular attapulgite. The co-administration of the drug with a 30 ml dose of a commercial antidiarrheal suspension containing 10% activated attapulgite and 3% colloidal attapulgite produced a relatively lesser effect; the reduction in extent of absorption being 40%. No statistically-significant effect was found when the adsorbent was ingested 2 h prior to the drug. The observed reduction in drug bioavailability in the presence of attqapulgite to the significant uptake of the drug by the adsorbent.