ABSTRACT
The aim of the investigation was to develop and evaluate thermoreversible in situ nasal gel formulations of repaglinide (REP) and to establish correlation between its in vitro release and ex vivo permeation profiles. The solubility of REP was enhanced by preparing solid dispersions (SDs) with hydrophilic carriers (PVP K30/ PEG 6000/ poloxamer 188) in different weight ratios. REP: PVP K30 (1:5) was selected as the optimized SD as it showed highest enhancement in solubility (405%). The optimized SD was characterized by SEM and DSC and incorporated into a blend of thermoreversible and mucoadhesive polymers (poloxamer 407 and carbopol 934 P) by cold technique to form in situ gels (F1-F6). The prepared in-situ gels were evaluated for various pharmacotechnical features and the formulation F3 exhibited least gelling time of 6.1± 0.20, good mucoadhesive property to ensure sufficient residence time at the site of application and a %CDR of 82.25%. The ex vivo permeation characteristics across goat mucosa can be summarized as CDP of 78.7%, flux = 6.80 mg/cm2/h; permeability coefficient of 2.02 mg/h and zero order kinetics. On correlating the CDR profile of F3 with that of its CDP profile, a R2 value of 0.991 (slope= 0.921) was observed. The value of slope approximating one, suggested that almost entire amount of drug released from F3 was capable of permeating across the nasal mucosa, ex-vivo indicating that in-situ nasal gels of REP for systemic action can be successfully developed for the management non-insulin dependent type-II diabetes mellitus.
ABSTRACT
The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal delivery of drug. Present investigation was aimed to develop a mucoadhesive in situ gel of Granisetron hydrochloride (GH) with reduced nasal mucocilliary clearance in order to improve the bioavailability of the antiemetic drug, granisetron hydrochloride. The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling Pluronic flake 127 (PF 127). Moringa gum (MG), carboxymethyl tamarind gum (CMTG) and sodium alginate (SA) was used to modulate mucoadhesion whereas drug release of optimized formulation was modified by 0.3% polyethylene glycol 6000 (PEG 6000). Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased and gelation temperature decreased significantly. Preformulation studies showed that addition of GH in 18% PF 127 gels modulated gelation temperature significantly while mucoadhesive polymers alters mucoadhesion. Formulation F6, F11 and F15 showed more than 80% of drug diffusion at 240 min. Gelation temperature and mucoadhesive strength of all three formulations were found in the range of 30-31 C and 963.66±9.60 to 991.33±10.26 dyne/cm2 respectively. Formulation F11 showed optimum results and further histopathological evaluation reveled formulation is safe for use. Addition of PEG 6000 increased drug diffusion in formulation F11 with flux 0.034 mg.cm2/min. This study concluded the potential use of CMTG as mucoadhesive in situ nasal gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved nasal bioavailability.