Abstract. The purpose of this work was to develop novel taste masked mouth-dissolving tablets of tramadol that overcomes principle drawback of such formulation which is inadequate mechanical strength. Tramadol is an opioid analgesic used for the treatment of moderate to severe pain. Mouthdissolving tablets offer substantial advantages like rapid onset of action, beneficial for patients having difficulties in swallowing and in conditions where access to water is difficult. The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time while maintaining a good mechanical strength of the tablet. Mouth-dissolving tablets of tramadol are not yet reported in the literature because of its extreme bitter taste. In this work, the bitter taste of Tramadol HCl was masked by forming a complex with an ion exchange resin Tulsion335. The novel combination of a superdisintegrant and a binder that melts near the body temperature was used to formulate mechanically strong tablets that showed fast disintegration. A 3 2 full factorial design and statistical models were applied to optimize the effect of two factors, i.e., superdisintegrant (crospovidone) and a mouth-melting binder (Gelucire 39/01). It was observed that the responses, i.e., disintegration time and percent friability were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste masked mouth-dissolving tablets of Tramadol HCl with adequate mechanical strength and rapid disintegration.

The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X 1), HPMC K100M (X 2), and dicalcium phosphate (X 3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y 1) and at 8th hour (Y 2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid.

Objectives: The objective of this work was to enhance the bioavailability of rizatriptan for brain targeted drug delivery through glutathione conjugated liposomes. Methods: Cholesterol glutathione conjugate was synthesized used as a rigidizing agent for liposomes. Liposomes with free cholesterol were also prepared for comparison. 9 batches each were prepared for glutathione conjugated liposomes and non-conjugated liposomes. All formulations were administered to rats. Results: For optimum nonconjugated liposomes batch particle size, drug release and entrapment efficiency were found to be 181nm, 90.2% and 88.1% respectively whereas the same values for glutathione conjugated batch were 194 nm, 84.9% and 86.4% respectively. Zeta potential was between 5 to 19. Polydispersity index was below 0.5. Scanning electron microscopy revealed slightly different shapes for both types of liposomes. These two types of rizatriptan liposomes and marketed oral tablet were administrated to rats to study plasma and brain levels. The t max for liposomes was faster (1 hr) as compared to the oral tablet. C max and AUC values for oral tablet, nonconjugated liposomes and conjugated liposomes were found to be 150.19 ng/ml and 223.99 ng.hr/ml; 320.55 ng/ml and 426.6 ng.hr/ml; 410.12 ng/ ml and 543.49 respectively. Maximum brain levels were achieved by glutathione conjugated liposomes over other liposomes and oral delivery (C max 310.46, 135.42 and 79.16 ng.ml respectively; AUC 786.94, 229.55 and 118.11 ng.hr/ml respectively). Drug targeting efficiency for conjugated liposomes was about 5 times higher. Conclusion: The study concluded that glutathione conjugated liposomes of rizatriptan administered by nasal transmucosal route can offer a promising approach to enhance targeted delivery to brain and bioavailability.

The objective of the present work was formulation, optimization and in-vivo evaluation of in-situ nasal gel of granisetron that shows liquid to gel transformation at nasal temperature (32-34°C) and maximum drug release after 4 hr; shows biovailability enhancement over oral delivery. Formulations were prepared using poloxamer PF 127 as gel forming polymer, carbopol as mucoadhesive agent and fulvic acid as penetration enhancer. A Box Benhken Design was used to prepare the experimental batches and Design Expert software for optimization of the formulation. Ex-vivo evaluations were carried out on sheep nasal mucosa and for in-vivo evaluation, rabbits were used. It was observed that optimized formulation showed gelation temperature near 33°C and drug release of 96% after 4hr. Fulvic acid was evaluated as penetration enhancer in this work and showed significant enhancement of drug diffusion across nasal mucosal membrane. Ex-vivo histological evaluation of nasal mucosa treated with optimized formulation showed no significant destructive effects. In-vivo evaluations showed that the plasma level profile of prepared insitu nasal gel was enhanced significantly over oral delivery. The findings suggested that nasal route nasal transmucosal delivery of granisetron can result in enhancement of its bioavailability over oral route.

Background: This work is based on the development of a wound healing dressing system for diabetic wounds using curcumin and syringic acid. A diabetic wound differs from a normal wound in respect to many pathophysiological changes. Therefore multiple issues like hemostasis, inflammation, cell proliferation and tissue remodeling need to be considered while selecting actives. A combination of curcumin, syringic acid and Aloe vera can address such aspects of pathophysiological changes in diabetic wound healing. Materials and Methods: Initially curcumin and syringic acid were mixed with Aloe vera juice. Carbopol 934 was used as a gelling agent for this mixture. This gel was loaded into sterilized polyurethane foam. The prepared dressing system was evaluated for in vitro and in vivo performance. Results: The dressing system showed excellent folding endurance. Ex vivo antibacterial activity was found to be excellent against Staphylococcus aureus and Escherichia coli. The zone of inhibition of developed foam dressing was found 25 ± 5 mm for Staphylococcus aureus and 20 ± 3 mm for Escherichia coli. In vitro diffusion was found to be 88.40% and 84.65 % for curcumin and syringic acid respectively. Diabetes induced rats were used for evaluating in vivo wound healing activity and complete wound healing was observed at the end of 14 days. Conclusion: Polyurethane foam dressing system based on curcumin, syringic acid and Aloe vera can show promising wound healing in diabetes conditions.