Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design.

OBJECTIVE: The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. METHODS: The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. RESULTS: SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. CONCLUSIONS: The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

Formulation development and evaluation of medicated chewing gum of anti-emetic drug.

CONTEXT: Medicated chewing gum (MCG) of Domperidone Maleate (DM) was developed by direct compression method with the goal to achieve quick onset of action and to improve patient compliance. OBJECTIVE: Formulation development of MCG of DM and optimization of the formulation by screening of different excipients. MATERIAL AND METHODS: MCG containing DM was prepared by screening different concentrations of sweeteners, flavouring agents, softening agents, lubricants and anti-adherents by changing one variable at a time. Performance evaluation was carried out by evaluating size, shape, thickness, taste, scanning electron microscopy, texture analysis, in vivo drug release study, ex vivo buccal permeation study and by studying statistical analysis for quality. RESULTS AND DISCUSSION: The statistical analysis showed significant improvement in organoleptic properties such as chewable mass, product taste, product consistency, product softness, total flavour lasting time and pharmaceutical properties like micromeritic properties after incorporation of appropriate excipients in an optimum amount in final optimized MCG formulation. In vivo drug release study showed 97% DM release whereas ex vivo buccal permeation study through goat buccal mucosa exhibited 11.27% DM permeation within 15 min indicating its potential for increasing bioavailability by decreasing time of onset. The optimized formulation showed good surface properties and the peak load required for drug release was found to be acceptable for crumbling action. CONCLUSION: The developed formulation of medicated chewing gum can be a better alternative to mouth dissolving and conventional tablet formulation. It may be proved as a promising approach to improve the bioavailability as well as to improve patient compliance.

Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design.

BACKGROUND: The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability. METHOD: The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3). RESULT: The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher. CONCLUSION: The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.

Mucoadhesive hydrogel films of econazole nitrate: formulation and optimization using factorial design.

The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 3(2) full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and "k" of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours.