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

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.

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.

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, Carr's index, Hausner's 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.

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.

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 (T(max)) 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 (f(2) = 96). Pores were observed following camphor sublimation. The pharmacokinetic studies proved F23 ability to increase extent of FXD absorption and reduce T(max).