Mahesh R. Dabhi

Novel approaches for stability improvement in natural medicines

Natural product market has seen tremendous growth in the last few years. It results in the formulation of a number of proprietary herbal products, majority of them being multi-component formulations. With the advancement of herbal drug treatments, it has now been observed that many of the constituents present in the drug may react with each other, raising the serious concern about the stability of such formulations which is an important issue in the field of phytochemistry and natural medicines. Natural products are often prone to deterioration, especially during storage, leading to loss of active component, production of metabolites with no activity and, in extreme cases, production of toxic metabolites. This area needs to be addressed in order to determine the efficacy of the formulation. Understanding the problems related to natural product stability can give the idea of dealing with the stability issues. Modifications of the conventional herbal formulations can deal with the stability problems to a large extent. This article deals with the stability problems and is aimed to provide some tools and techniques to increase stability of natural medicines and herbal formulations.

Application of Simplex Lattice Design and Desirability Function for the Formulation Development of Mouth Dissolving Film of Salbutamol Sulphate

The aim of the present investigation was to prepare and optimize the formulation of mouth dissolving film of salbutamol sulphate by applying experimental design technique. The films were prepared using hydroxypropyl methylcellulose, polyvinyl pyrrolidone and polyvinyl alcohol by solvent evaporation technique. Simplex lattice design and desirability function were adopted for the preparation of film possessing desirable and optimized characteristics. Tensile strength, elastic modulus, percentage strain, load at yield, and percentage drug release were selected as dependent variables. Regression equations and contour plots were used to relate the dependent and independent variables. The concept of similarity factor S(d) was used to prove similarity of dissolution between distilled water and simulated saliva (pH = 6.8). The polymers greatly influenced the mechanical properties and % drug release from the film. From the computed value of desirability function, it was determined that the film containing hydroxypropyl methylcellulose and polyvinyl alcohol was the best batch. The experimental design serves to be a useful tool for the formulation development of mouth dissolving film.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1–0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

Design of a Potential Colonic Drug Delivery System of Mesalamine

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit® S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.

Formulation, optimization and characterization of candesartan cilexetil nanosuspension for in vitro dissolution enhancement

According to Biopharmaceutical classification system (BSC), candesartan cilexetil (CC) is a class-II drug which has limited bioavailability mainly due to its low solubility. In order to enhance its solubility, a universal approach of making nanosuspension is been used in the present investigation. High pressure homogenization, controlled precipitation, media milling and high speed homogenization are the various approaches which are most widely used to produce the nanosuspension. Here, nanosuspension is formulated by combination of two approaches; high speed homogenization and media milling to expedite and ease the process. The polymers used to stabilized the nanoparticles were polyvinylpyrrolidone K-30 (PVP K30), poloxamer 407, HPMC E 50. To optimize the concentration of the polymer and surfactant the simplex lattice design is used. Various process parameters like homogenization speed, time, media milling cycle, drug to bead ration are optimized by changing one parameter at a time. The nanoparticles produced were of particle size less than 500 nm and were also found to be stable. The saturation solubility was enhaced more than 20 times than the bulk drug. The nanonization of the particles by combination of high speed homogenization and media milling is an effective method of enhancing in vitro dissolution of Candesartan cilexetil.

Optimization of Novel Mucoadhesive In Situ Film Forming Periodontal Drug Delivery System for Chemotherapeutic Agents

IntroductionThe objective of the present investigation was to develop and evaluate mucoadhesive in situ film forming periodontal drug delivery system (MIFPDDS) for local delivery of chemotherapeutic agents. Ethyl cellulose, a film forming release retardant, was used in combination with Eudragit RL100, a mucoadhesive polymer, and polyvinylpyrrolidone K-30 to develop MIFPDDS.Materials and methodsA simplex lattice design was employed to achieve an optimum solvent blend (N-methyl-2-pyrrolidone, polyethylene glycol-200, and propylene glycol) which has rapid film formation capacity and low viscosity. The prepared MIFPDDS was evaluated for various parameters such as in vitro film forming capacity, viscosity, in vitro diffusion study, ex vivo mucoadhesion study, stability study, and compatibility. A 32 full-factorial design was used to investigate the influence of formulation variables.Results and discussionDrug release data from all formulations were fitted to different kinetic models, and the Korsmeyer–Peppas model was found the best fit model. Increasing the concentration of each polymeric component increases viscosity, and time for 50, 70, and 90 % drug release was observed and graphically represented by the surface response and contour plots. The formulation of batches MIF1—PCM4, MIF6, and MIF7 failed to give the desired results for the first hour drug release and MIF8 and MIF9 failed to show viscosity below 70 cPs.ConclusionThe formulation of batch MIF5 containing 3 % (w/v) of ethyl cellulose and 8 % (w/v) of Eudragit RL100 was considered as optimum formulation.