Nabila Ahmed Boraie

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.

Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori.

The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol(®) and Compritol(®) were incorporated into G-based formulations (G1%C1%). Mz:lipid ratio was 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing. Alg4%C2% FRS exhibited short gelation lag time (3s), long duration (>24h), floating lag time 1m in and duration >24h, and a reliable sustained drug release (MDT 6h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz:GMS 1:1) enhanced the gelation lag time and duration (6s and >24h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori.

Nebulized solid lipid nanoparticles for the potential treatment of pulmonary hypertension via targeted delivery of phosphodiesterase-5-inhibitor.

Phosphodiesterase type 5 (PDE-5) inhibitors - among which sildenafil citrate (SC) - play a primary role in the treatment of pulmonary hypertension (PH). Yet, SC can be only administered orally or parenterally with lot of risks. Targeted delivery of SC to the lungs via inhalation/nebulization is mandatory. In this study, solid lipid nanoparticles (SLNs) loaded with SC were prepared and characterized in terms of colloidal, morphological and thermal properties. The amount of drug loaded and its release behavior were estimated as a function of formulation variables. The potential of lipid nanocarriers to retain their properties following nebulization and autoclaving was investigated. In addition, toxicity aspects of plain and loaded SLNs on A549 cells were studied with respect to concentration. Spherical SLNs in the size range (100-250nm) were obtained. Particles ensured high encapsulation efficiency (88-100%) and sustained release of the payload over 24h. Cell-based viability experiments revealed a concentration-dependant toxicity for both plain and loaded SLNs recording an IC50 of 516 and 384μg/mL, respectively. Nebulization with jet nebulizer and sterilization via autoclaving affected neither the colloidal stability of SLNs nor the drug entrapment, proving their potential as pulmonary delivery system. Interaction of SLNs with mucin was a function of the emulsifier coating layer. Results yet seeking clinical evidence - might give promises of new therapy for PH of higher safety, better performance and higher patient compliance.

Alendronate-loaded, biodegradable smart hydrogel: a promising injectable depot formulation for osteoporosis

Abstract Alendronate (ALN) is a BCS III bone resorption inhibitor, with very poor oral bioavailability. Our approach is to develop a minimally invasive thermogelling system for prolonged local delivery of ALN. For this, different chitosan-based thermogels were developed and characterised in terms of gelation time, injectability, pH, viscosity and thermoreversibility. Chitosan/β-glycerophosphate (CS/βGP) hydrogel pursued temperature-dependent, thermoreversible gelation behaviour and was thus selected for drug loading. Increasing ALN concentration resulted in hydrogels with lower porosity and higher density. FTIR and DSC proved interaction between ALN, CS with βGP. CS/βGP hydrogel ensured controlled ALN release over 45–65 days depending on initial ALN loading. Freeze drying improved the shelf-life stability with minor impact on thermogelling character. In vivo injection of plain and ALN-loaded hydrogel in rats rapidly gelled 15 min post-injection. Based on histological examination, ALN-loaded thermogel showed less inflammatory response, faster proliferation and maturation of granulation tissue relative to plain thermogel. Hydrogels excised 21-days post-injection proved the biocompatibility and biodegradability of the system. The presented chitosan-based thermogel has significant positive attributes for site-specific, time-controlled, intra-articular delivery of ALN.

In vitro availability of promethazine-HCl in the presence of some commercial antacids

Abstract The dialysis and dissolution dialysis rates of promethazine-HCl alone or in the presence of 4 commercial antacid suspensions and 3 commercial antacid powders in either 0.1 HCl or distilled water, was studied at 37° C. The commercial products caused a substantial decrease in the percentage drug dialyzed especially in water. Adsorption, viscosity effects as well as pH effects on both the drug and ingredients of the formulations, may be responsible for the observed decrease in the dialytic rate constant. Adsorption experiments on the main ingredients of the products were carried out. Kaolin showed a high adsorption power for the drug in both HCl and water; bismuth carbonate had a much higher adsorption capacity in HCl than in water while aluminium hydroxide showed a rather low adsorption property especially in HCl. The clinical significance of such interactions needs further biological investigation.

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.

Nanostructured lipid carriers versus solid lipid nanoparticles for the potential treatment of pulmonary hypertension via nebulization

&NA; With the non‐selective vasodilating action, short half‐life and first‐pass metabolism of sildenafil (SC), local application in the lung for pulmonary arterial hypertension is of high demand. Although several nanosystems have been lately investigated, nanostructured lipid carriers (NLCs) give promises of potential safety, biodegradability and controlled drug release. In the current study, NLCs comprising either precirol, stearic acid or beeswax as solid lipid in presence of oleic acid as liquid lipid and PVA or poloxamer as emulsifier were prepared. Optimized NLCs (200–268 nm in size) were appraised versus SLNs both in vitro and in vivo. Precirol/PVA‐based SLNs and NLCs ensued high entrapment efficiencies (EE > 95%) and controlled release behaviour over 6 h even though NLCs showed higher release profile. Stability studies at 4 °C indicated potential colloidal and entrapment stability over 3 months. Interestingly, NLCs demonstrated efficient nebulization, low interaction with mucin and higher viability of A549 cells (3‐fold increase in IC50 relative to SLNs) providing good aptitudes for pulmonary application. In vivo administration of free SC in rats revealed localized intra‐alveolar bleeding, presumably related to excessive vasodilatation. Meanwhile, the nanoencapsulated drug confirmed normal lung parenchyma with minimal incidence of bleeding. Inspiring results highlight the potential of sildenafil‐laden nanostructured lipid carriers as pulmonary drug delivery system.

Stability and Bioavailability of Five Brands of Ampicillin Suspensions Following Reconstitution

AbstractThe stability of the active ingredient of four generically equivalent brands of ampicillin for oral suspension were studied at three controlled conditions 5,25 and 40°C. All ampicillin suspensions tested, except one brand, did not meet the official compendial stability requirements when stored at the recommended conditions. However the different brands studied were not completely equivalent with respect to stability. In vitro release of ampicillin from 5 brands of ampicillin suspension was studied by using dialysis method. Slight differences in dissolution profiles among the studied brands were observed. The bioavailability of 5 brands of ampicillin suspensions was examined in 5 subjects using cross-over experimental design. Based upon the urinary excretion method, the extent and rate of ampicillin bioavailability were determined. Statistically significant differences were found between the brands examined. An insignificant intersubject variation was found between the volunteers participated in th...