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Purpose: The objective of the present investigation was to fabricate a thermosensitive gel containing paliperidone loaded microspheres for the treatment of schizophrenia for brain delivery through nasal route. Incorporation of drug in to microspheres and then in to gel should increase the duration of release and nasal duration time respectively. Material and Method: Ethyl cellulose microspheres containing paliperidone palmitate were prepared by emulsification of ethyl acetate dispersion containing polymer and drug with aqueous external phase containing polysorbate 80. Amount of ethyl cellulose and polysorbate 80 were identified as critical formulation variables influencing the drug release at critical time points, percentage yield and particle size. These factors were studied using 2 factors and 3 level face centered factorial design using Design Expert®. Drug-excipient compatibility was ascertained using FTIR analysis. The paliperidone microspheres were then incorporated in to Pluronic F127 and HPMC gel having required thermo sensitive and muco adhesive properties. Gel containing microspheres was subjected to Ex vivo permeation study, irritation study using sheep nasal mucosa and pharmacodynamic study (spontaneous motor activity in mice). Results: Microspheres that could sustain the drug release up to 8 hours were developed. Thermoreversible gel having required thermo sensitive and muco adhesive properties was developed. The Ex vivo permeation study and pharm a codynamic study of the drug loaded microsphere containing gel confirmed the release up to 8 hours. The histopathology study showed absence of irritation on sheep nasal mucosa. Conclusion: Paliperidone palmitate loaded microspheres containing gel could prolong and target the drug release to brain and therefore give prolonged and intense action. [ABSTRACT FROM AUTHOR]

Objective: To develop a gastro retentive in situ oral gel to improve the bioavailability of the cephalosporin antibiotic drug, Cefuroxime Axetil. Methodology: Sodium alginate and pectin were the ionic dependent gel forming polymer. Calcium chloride was used as complexing agent to increase cross linking along with sodium citrate. Mucoadhesion was enhanced with the help of polymer HPMC K4M. Two factors and three levels factorial design was used for the optimization of formulation using design expert software version 7.1.6. The In situ gel system was evaluated for the content uniformity, pH, gelling capacity, viscosity of gel, invitro drug release and mucoadhesion study. Results and Discussion: Optimized formula showed more than 24% Drug release after 1 hour and prolonged release up to 12 hour, Viscosity of gel formed was 6423.9 cps and 3.668 N/cm². The results revealed that as the concentration of Sodium alginate was directly proportional to mucoadhesion, inversely proportional to drug release while concentration of pectin directly proportional to drug release. Conclusion: The study point to the potential of in situ oral gel in terms of ease of administration, better patient compliance and prolonged gastro-retention. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. [ABSTRACT FROM AUTHOR]