Abstract. In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2 3 factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q 1 A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.

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A nondisintegrating, controlled release, asymmetric membrane capsular system of flurbiprofen was developed and evaluated for controlled release of the drug to overcome some of its side effects. Asymmetric membrane capsules were prepared using fabricated glass mold pins by phase inversion process. The effect of different formulation variables was studied based on 2(3) factorial design; namely, level of osmogen, membrane thickness, and level of pore former. Effects of polymer diffusibility and varying osmotic pressure on drug release were also studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. Differential scanning calorimetry studies showed no incompatibility between the drug and the excipients used in the study. In vitro release studies for all the prepared formulations were done (n = 6). Statistical test (Dunnett multiple comparison test) was applied for in vitro drug release at P > .05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 92.94. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed the Higuchi model and the mechanism of release was Fickian diffusion.

In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with L-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug.

Abstract. The purpose of this study was to develop a dosage form that was easy to administer and provides rapid release of the drug roxithromycin, using modified polysaccharides as rapidly disintegrating excipients. Modified polysaccharides co grinded treated agar (C-TAG) and co grinded treated guar gum (C-TGG) were prepared by subjecting pure polysaccharides namely agar and guar gum respectively to sequential processes of wetting, drying and co grinding with mannitol (1:1). The modified polysaccharides were characterized by Scanning Electron Microscopy and Diffuse Reflectance Spectroscopy and evaluated for particle size distribution, derived properties, swelling index and biodegradability. Optimization studies based on 2 2 factorial designs, with friability and disintegration time as response parameters were used to formulate orodispersible tablets of roxithromycin and evaluated for wetting time, water absorption ratio and in vitro drug release at salivary pH 6.4 and physiological pH 7.4. Results indicated that lower levels of modified polysaccharides namely C-TAG in F 3 and C-TGG in F 7 and higher levels of microcrystalline cellulose, exhibited least disintegration times without friability concerns. In vitro release of optimized formulations F 3 and F 7, both at salivary pH and physiological pH was found to be more than 90% within 30 min as compared to 27.82% at the same time point of conventional formulation. Stability studies carried out as per ICH Q1A guidelines suggested the formulations to be stable for a period of 6 months. Thus the approach of using modified polysaccharides as fast disintegrating excipient can be used to formulate a stable orodispersible formulation.