Krishna Sanka

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. Results: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis

Abstract Context: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. Objective: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. Methods: A 3-factor, 3-level Box–Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. Results: The particle size and encapsulation efficacy of these microspheres were 117.36 ± 10.54 µm and 85.06 ± 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation reveled delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund’s adjuvant-induced arthritis rats. Conclusion: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.

Enhancement of solubility, dissolution release profile and reduction in ulcerogenicity of piroxicam by inclusion complex with skimmed milk

Abstract Context: Piroxicam (PXM), a non-steroidal anti-inflammatory drug which is poorly soluble in water and ulcerogenic. Milk has been used against the gastric disturbances caused by non-steroidal anti-inflammatory drugs. In this study, skimmed milk (SKM) is used as the carrier for inclusion complex (IC) due to its surface active agent and amino acid content. Purpose: To enhance the solubility, dissolution rate and prevent ulcerogenicity of PXM though IC with SKM. Methods: IC of PXM were prepared with SKM by solvent evaporation method using rota evaporator and were evaluated for solubility, dissolution, solid state characterization, drug excipient interaction, rat intestinal permeation, ulcerogenicity and histopathological studies. Results: Solubility of PXM was enhanced 2.5 times with IC. The dissolution release and amount of PXM permeated through rat small intestine was enhanced significantly with IC. Decreases in the gastric lesion index values of IC were observed than physical mixture (PM) and free PXM. The histopathological studies revealed significant reduction in ulceration in rat stomach after treatment with IC. Conclusion: It is concluded that SKM is a good carrier to prepare IC of PXM for oral administration.

Colon-Specific Microparticles of Piroxicam: Formulation and Optimization Using 32 Factorial Design

The aim of the present study was to prepare and evaluate colon-specific microparticles of piroxicam by oil/water emulsion solvent evaporation method. A 32 factorial design was employed to study the combined influence of two independent variables amount of piroxicam (X1) and amount of eudragit S-100 (X2) on dependent variables, encapsulation efficacy (Y1), percentage cumulative drug release at the fifth hour (Y2), and percentage cumulative drug release at the tenth hour (Y3). The microparticles were evaluated for micromeritic properties and drug release studies. Drug–polymer interaction was determined by differential scanning calorimeter, x-ray powder diffraction. The surface morphology and spherocity was studied by scanning electron microscopy. The developed piroxicam microparticles showed desired colon-specific delivery.

Improved anti-diabetic activity of glibenclamide using oral self nano emulsifying powder.

Abstract The objective of the present study was to improve solubility, dissolution rate and therapeutic efficacy of a BCS Class II drug, glibenclamide by using oral self nano emulsifying powder. The powder was prepared by adsorbing the mixture of oil, surfactant and co-surfactant onto a carrier with large surface area; Aerosil 200. The ratios of oil and Smix (surfactant/co-surfactant mixture) required to produce an emulsion was optimized based on percentage transmittance studies and particle size determinations. The optimized formulation was subjected to in vitro dissolution study and in vivo therapeutic efficacy in rabbits by monitoring blood glucose levels. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction studies revealed that the drug was present in amorphous form in the final formulation. The in vivo study in rabbits indicated the improved therapeutic efficacy of glibenclamide in self-nanoemulsifying powder compared to plain drug.

Enhanced oral delivery of risperidone through a novel self-nanoemulsifying powder (SNEP) formulations: in-vitro and ex-vivo assessment

Abstract Context: The oral delivery of risperidone encounters a number of problems, such as pH dependent solubility and low bioavailability, due to its lipophilicity and aqueous insolubility. Objective: To improve the solubility, dissolution and intestinal permeation thereby bioavailability of risperidone through a novel self-nanoemulsifying powder (SNEP) formulations. Materials and methods: Oleic acid, Tween® 20, PEG 600 and Aerosil® 200 were chosen as oil, surfactant, co-surfactant and carrier, respectively from solubility and emulsification studies. Ternary phase diagram was constructed to determine emulsifying region. Results and discussion: The Z-average and polydispersity Index of developed formulation was 83.1 nm and 0.306, respectively. Ex vivo permeation studies on isolated rat intestine indicated that the amount of risperidone permeated from SNEP formulation was increased around 4- and 1.8-fold than that of pure drug and marketed formulation, respectively. Conclusion: This developed SNEP formulations can be regarded as novel and commercially feasible alternative to the current risperidone formulations.

Improved Solubility and Dissolution Release Profile of Lurasidone by Solid Self-Nanoemulsifying Drug Delivery System

Abstract The purpose of the study was to investigate self-nanoemulsifying drug delivery system (SNEDDS) as potential delivery system for poorly water soluble drug Lurasidone (LUR). SNEDDS was formulated using oil (Anise oil) surfactant (Tween® 80), and co-surfactant (Polyethyleneglycol-600). Z-average size, PDI and in-vitro drug release were considered to screen and optimize the composition of liquid-SNEDDS. Following emulsification, the optimized formulation was selected to have the smallest mean particle size and highest absolute zeta potential, which would yield stable emulsion. Scanning electron microscopy, X-ray powder diffraction studies confirmed that there was no crystalline drug in Solid-SNEDDS. Fourier transform infrared (FTIR) spectroscopy study revealed that there was no measurable chemical interaction of drug with the carrier. There was no significance difference in zeta average, zeta potential, and release profile of developed formulation before and after stability study. Both Liquid-SNEDDS and solid-SNEDDS showed improved in-vitro drug release than the pure drug. This paper provides an overview of the SNEDDS of LUR as a promising alternative to improve solubility and dissolution release profile. The results suggested that the SNEDDS could be used as an effective oral dosage form to improve the oral delivery of poorly water soluble drug LUR.