The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8:2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1:1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t 90 , 60 seconds) in SGF compared with marketed formulation (t 90 , 240 seconds; P G .01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity.

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Mucoadhesive temperature-mediated in situ gel formulations using chitosan and hydroxyl propyl methyl cellulose were used to enhance intranasal (i.n.) delivery of the dopamine D2 agonist ropinirole to the brain. Formulations were tested for gelation time, thermosensitivity, mucoadhesion, in vitro release and permeation, in vitro cytotoxicity, nasal clearance, in vivo bioavailability and brain uptake. In vivo bioavailability and brain uptake of ropinirole were assessed in albino rats following intranasal administration of 99mTc-ropinirole in situ gel, intranasal ropinirole solution and intravenous (i.v.) ropinirole solution. Radiolabeled ropinirole uptake was calculated as a fraction of administered dose. The absolute bioavailabilty of ropinirole from the temperature-mediated in situ gelling nasal formulation was 82%. The AUC (0-480 min) in brain after nasal administration of ropinirole in situ gel was 8.5 times (869 +/- 250% x min/g versus 102 +/- 20% x min/g) that obtained following i.v. administration, this value was also considerably higher (869 +/- 250% x min/g versus 281 +/- 52% x min/g) than that achieved with intranasal ropinirole solution. High brain direct drug transport percentage (DTP; 90.36%) and drug targeting index (DTI) > 1 confirms direct nose to brain transport of the intranasal in situ gel formulation of ropinirole.

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Incompetence of antiretrovirals (ARV) in complete eradication of HIV from the CNS is the biggest issue in neuro-AIDS treatment. The ineffectiveness is largely due to the poor penetration of ARV. Hence, the present study is attempted to enhance the CNS uptake of efavirenz (EFV) by designing intranasal EFV nanoparticles (EFV-NPs). EFV-NPs were fabricated using chitosan-g-HPβCD by ionic gelation method and optimized using quadratic response surface methodology (RSM) employing two-factor, five-level circumscribed central composite design. NPs containing drug: polymer ratio (1.25:0.79) were spherical with 198 ± 4.4 nm size, 23.28 ± 1.5% drug loading and 38 ± 1.43% entrapment efficiency. NPs showed sustained drug release (99.03 ± 0.30% in 8 h) and followed Fickian diffusion mechanism. It gave 4.76 times greater permeability than plain drug solution through porcine nasal mucosa. Enhanced CNS bioavailability (12.40-fold that of i.v solution) of EFV, high drug-targeting percentage (99.24%) and drug-targeting index (141.3) post-intranasal administration of NPs was observed. These results are corroborated by gamma scintigraphy images, which revealed high CNS uptake. NPs appeared histocompatible with porcine nasal mucosa and non-toxic to L929 cell line. Thus, CS-g-HPβCD served as a potential carrier in developing intranasal mucoadhesive EFV-NPs for the CNS targeting.