The present research work was designed to formulate and evaluate carbamazepine (CBZ) loaded nanostructured lipid carrier (NLC) based in-situ gel for nasal delivery. Methods: The NLC formulation of CBZ was prepared by microemulsion technique followed by probe sonication and evaluated for particle size, zeta potential, entrapment efficiency and in vitro drug diffusion. NLC formulation was incorporated into in-situ gelling formulation using poloxamer 407 (P407), poloxamer 188 (P188) and mucoadhesive polymer. The effect of concentration of poloxamer 188 (X 1), type of mucoadhesive polymer (X 2) and concentration of mucoadhesive polymer (X 3) on gelling temperature (Y 1) and drug diffusion after 8 h (Y 2) was studied using Box-Behnken design. In vivo anticonvulsant activity of optimized formulation was studied in Wistar rats by maximal electro-convulsion model (MES). Results: The optimized CBZ NLC formulation, with 20% drug loading, 0.5:1 as Precirol:Capmul MCM ratio as lipid phase and 1:3 as Lipid:Smix ratio, resulted in 89.73±0.2% drug entrapment, 55.95±1.09% of drug diffusion after 8 h, particle size of 132.8 nm with polydispersity index of 0.302 and zeta potential of-29.2±6.1 mV. The in-situ gel formulation with 20% P407, 5% P188 and 0.2% chitosan was optimized and demonstrated excellent gelling ability, gelling temperature in the range of 30 to 35°C, 42.46% of drug diffusion in 8 h by Fickian diffusion mechanism and 31.34±0.76% of drug permeation through sheep nasal mucosa. In vitro anticonvulsant activity in MES model in rat demonstrated significant efficacy (71.95% protection against seizure in extension phase) as compared to plain in-situ nasal gel (50.26% protection against seizure in extension phase). Conclusion: NLC based in-situ gelling formulation demonstrated its potential for nasal delivery of CBZ with improved anticonvulsant activity.

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The bioavailability of drugs from conventional ophthalmic formulations is low. To optimize the therapy, sustained release ophthalmic dosage forms are warranted. Hydrogels such as sodium-carboxymethyl cellulose, hydroxypropylmethyl cellulose, Carbopol-940, Carbopol-941 and Lutrol-FC-127 increase the duration of action of various drugs. Gels containing pilocarpine were prepared and evaluated by measuring the intensity and duration of miotic response in albino rabbits. Carbopol-940 gels, being the best of those used, were studied further for the effect of its concentration and of additives (benzalkonium chloride, phenylmercuric nitrate, chlorbutol and disodium edetate), autoclaving at 121 degrees C for 30 min and irradiation with gamma rays (2.5 Mrad), on the end product.

3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to areceptors (25 nM) in the presence of 25 nM splperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10~9 to 10~2 M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N, N'-dimethy1-2-phenylethylamine) , yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50=900 nM). Applying the technic of Bromberg [Exp. Eye Res. , 40:313-320, 1985] , in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds, in vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10~8 to 10"4 M for various derivatives of bromhexine and ÎO-4 M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50/il) to the right eye of New Zealand white rabbits (n=20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10"'' M) , with haloperidol (lO"4 M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a doseresponse curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.