Soad A. Yehia

Fluconazole mucoadhesive buccal films: in vitro/in vivo performance.

Fluconazole mucoadhesive buccal films were prepared using film forming polymers namely; hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), chitosan, Eudragit and sodium alginate (SALG) either alone or in combination with bioadhesive polymers. The bioadhesive polymers studied were sodium carboxymethyl cellulose (SCMC), Carbopol 974P, and polycarbophil (AA-A). The prepared films were characterized by means of film thickness, surface pH, swelling capacity, in vitro adhesion, in vivo residence time, in vitro drug release and in vivo drug release to determine the amount of drug release from selected film formulae using microbiological assay and HPLC. Optimum release behavior, convenient bioadhesion, acceptable elasticity were exhibited by film containing 2% HPMC and 1% SCMC (fresh or stored for 6 months). Determination of the amount of drug released in saliva after application of the selected fluconazole films confirmed the ability of the film to deliver the drug over a period of approximately 300 minutes and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.

Biodegradable donepezil lipospheres for depot injection: optimization and in-vivo evaluation

Objectives  The purpose of this study was to develop an injectable depot liposphere delivery system with high loading capacity for controlled delivery of donepezil to decrease dosing frequency and increase patient compliance.

Phenylalanine-free taste-masked orodispersible tablets of fexofenadine hydrochloride: development, in vitro evaluation and in vivo estimation of the drug pharmacokinetics in healthy human volunteers

Abstract Context: Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 h (Tmax) post-dose. Objective: Developing taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Methods: Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (croscarmellose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting, disintegration and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant (Pruv®), visualized via scanning electron microscopy and evaluated for FXD pharmacokinetics in healthy volunteers relative to Allegra® tablets. Results: Based on gustatory sensation test, FXD–CS (1:1) and FXD–ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties. Drug release profiles of F23 and the phenylalanine-containing Allegra® ODT were similar (f2 = 96). Pores were observed following camphor sublimation. The pharmacokinetic studies proved F23 ability to increase extent of FXD absorption and reduce Tmax.

Pulsatile systems for colon targeting of budesonide: In vitro and in vivo evaluation

The purpose of this study is to increase the lag time and prevent release of budesonide, a corticosteroid drug used in Crohn’s disease for the first 5 h and efficiently deliver it to the colon. Eudragit S100 spray-coated capsules and pulsatile systems using tablet plugs of cellulose acetate butyrate (CAB), HPMC K4M, guar gum, and pectin were prepared. Eudragit S100-coated capsules released 80.62% after 5 h. In pulsatile systems, decreasing the ratio of the polymer significantly increased the rate and extent of drug release. Spray-coating with EUD S100 decreased the extent of drug release to 48.41%, 69.94%, 80.58%, and 45.23% in CAB, HPMC K4M, pectin, and guar gum, respectively; however, the entire amount was released in the target area. In the presence of bacterial enzymes, selected formulas showed nearly 100% release. X-ray imaging performed to monitor the capsules throughout the GIT in human volunteers of the capsules and spray-coated pulsatile systems with 25% guar gum in the plug showed bursting in the transverse and ascending colon, respectively. Both formulations showed marked reduction in induced rabbit colitis model.

A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery

One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1–24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.

Enhancement of the Oral Bioavailability of Fexofenadine Hydrochloride via Cremophor(®) El-Based Liquisolid Tablets.

PURPOSE The current work aimed to develop promising Fexofenadine hydrochloride (FXD) liquisolid tablets able to increase its oral bioavailability and shorten time to reach maximum plasma concentrations (Tmax). METHODS Eighteen liquisolid powders were developed based on 3 variables; (i) vehicle type [Propylene glycol (PG) or Cremophor(®) EL (CR)], (ii) carrier [Avicel(®) PH102] to coat [Aerosil(®) 200] ratio (15, 20, 25) and (iii) FXD concentration in vehicle (30, 35, 40 %, w/w). Pre-compression studies involved identification of physicochemical interactions and FXD crystallinity (FT-IR, DSC, XRD), topographic visualization (SEM) and estimation of flow properties (angle of repose, Carrs index, Hausners ratio). CR-based liquisolid powders were compressed as liquisolid tablets (LST 9 - 18) and evaluated for weight-variation, drug-content, friability-percentage, disintegration-time and drug-release. The pharmacokinetics of LST-18 was evaluated in healthy volunteers relative to Allegra(®) tablets. RESULTS Pre-compression studies confirmed FXD dispersion in vehicles, conversion to amorphous form and formation of liquisolid powders. CR-based liquisolid powders showed acceptable-to-good flow properties suitable for compaction. CR-based LSTs had appropriate physicochemical properties and short disintegration times. Release profile of LST-18 showed a complete drug release within 5 min. CONCLUSION LST-18 succeeded in increasing oral FXD bioavailability by 62% and reducing Tmax to 2.16 h.

Formulation and evaluation of injectable in situ forming microparticles for sustained delivery of lornoxicam

Abstract The objective of this study is to formulate biodegradable in situ microparticles (ISM) containing lornoxicam for post-operative and arthritic pain management. ISM emulsions were prepared according to 25 full factorial experimental design to investigate the influence of formulation variables on the release profile of the drug. The independent variables studied are the polymer type, polymer inherent viscosity, polymer concentration, oil type and polymer:oil ratio. In vitro drug release, microscopical examination, particle size determination and syringeability measurement were selected as dependent variables. The effect of γ-sterilization on the prepared formulae was also examined. The prepared formulae showed extended drug release over two weeks, and flow time below 5 s/ml. Scanning electron microscope revealed that the prepared microparticles were spherical in shape, with diameter ranging from 3.45 to 22.78 µm. In vivo pharmacokinetic evaluation of two selected optimum formulations in rabbits showed prolonged drug absorption indicated by delayed Tmax and the extended mean residence time. In conclusion, the prepared injectable ISM could be a promising approach for providing extended delivery of lornoxicam with low initial burst effect.

Real time stability and viability prediction of the anticancer BCG after lyophilization

Abstract To test if trehalose could be a better cryoprotectant for BCG than the usually used lactose and predict viability of BCG during shelf-life, BCG was suspended into three stabilizer systems containing 15% w/v trehalose, trehalose–gelatin mixture (in ratio, 30:1 w/w) or lactose. Each formula was lyophilized and several quality parameters were tested before and after lyophilization including sterility, safety, viability, morphology and moisture content. Samples of lyophilized formulae were tested for their reconstitution time and others were charged to stability chambers at 5 °C for the performance of real time study. Shelf-life of each formula was estimated and correlation between moisture content and loss in viability was established at each time interval of the real time stability study. Sterility, safety and morphology were retained after lyophilization. Just after lyophilization, minute diminish in viability was observed in the presence of each stabilizer (0.02–0.05%). There was no significant difference in reconstitution time of the three lyophilized formulae. Lactose BCG had the highest shelf-life among the used cryoprotectants during the real time stability studies. Also, moisture content was highly correlated to viability with correlation coefficient ranged between 0.97 and 0.99 and so, the former could be used for prediction of viability throughout the vaccine shelf-life.

Zaleplon loaded bi-layered chronopatch: A novel buccal chronodelivery approach to overcome circadian rhythm related sleep disorder

&NA; The aim of this study was to develop a novel buccal bi‐layered chronopatch capable of eliciting pulsatile release pattern of drugs treating diseases with circadian rhythm related manifestation. Zaleplon (ZLP) was used as a model drug intended to induce sleep and to treat middle of night insomnia. The chronopatch was prepared adopting double casting technique. The first layer was composed of a controlled release patch containing ZLP‐Precirol melt granules intended to release ZLP in a sustained manner to maintain sleep and to prevent early morning awakening. The second layer was composed of a fast release lyophilized buccal disc containing ZLP loaded SNEDDS (Z‐SNEDDS) intended for rapid sleep induction. Pharmacokinetic parameters of ZLP from the chronopatch were compared to those of the immediate release capsule, Siesta®, as reference in Mongrel dogs using a randomized crossover design. The appearance of two peaks having two Cmax and Tmax proved the pulsatile release pattern. The increase in relative bioavailability of ZLP from the chronopatch was 2.63 folds. The results revealed the ability of the developed ZLP loaded bi‐layered chronopatch to be a candidate for overcoming early morning awakening without middle of night dose administration.

Polymeric and Non Polymeric Injectable In-Situ Forming Implant Systems for Sustained Delivery of Lornoxicam: In Vitro and In Vivo Evaluation.

OBJECTIVE Formulation of injectable In situ forming implant (ISI) systems of lornoxicam for dental and postoperative pain management to decrease dosing frequency and increase patient compliance. METHODS Polymeric in situ implant solutions were prepared using different concentrations and inherent viscosities of Poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG) using 22X4 factorial experimental design. Nonpolymeric systems were prepared using different concentrations of lipids like cetyl alcohol and stearyl alcohol and also sucrose acetate isobutyrate (SAIB) using 32 factorial experimental design. In vitro release study, rheological measurement, syringeability assessment and effect of γ-sterilization were used for evaluation of the prepared formulae. In vivo pharmacokinetic study of lornoxicam from the most optimum formula was conducted in a rabbit model using HPLC analysis of blood samples. RESULTS Polymeric systems showed high burst release followed by very slow release rate over 72 hours. Formula I 24 (containing SAIB 80% (w/w)) showed relatively low burst release followed by diffusion controlled release pattern, low viscosity, Newtonian flow behavior and good syringeability. γ- sterilization had no significant effect on the in vitro release and the physical nature of the most optimum formula. In vivo study concluded that intramuscularly injected In situ implant formula I 24 showed prolonged release pattern compared to the marketed product which was indicated by the increased Tmax and the extended mean residence time. CONCLUSION Lornoxicam ISI systems could be promising as convenient injectable sustained release delivery systems for dental and postoperative pain management.