Effect of particle size and diluent type on critical parameters for disintegration of tablets containing croscarmellose sodium as a disintegrant

Purpose: The aim of the present work was to determine the effect of particle size and type of diluents on critical concentration for the disintegration of tablet formulations containing a physical binary mixture of a superdisintegrant (croscarmellose sodium, CS) and a diluent.Methods: The diluents used in this study were microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP) and pregelatinized starch (PGS). Each diluent was divided into 2 different size ranges (small and large size)) and further mixed with 0 - 100 % CS. The binary mixture was compressed at controlled pressure, and the disintegration time and physical characteristic of the tablets were evaluated.Results: The point of CS concentration that markedly affected the disintegration time of the tablets was recorded as the critical concentration for disintegration. The results showed that the particle size of the diluent did not affect the disintegration time. The critical CS concentrations were 2 % for DCP and MCC tablets and 5 % for PGS tablet. Adding a small amount of CS improved the disintegration of the tablets. However, increasing the amount of CS in the formulation also affected the hardness of the tablets. The particle size of diluents had a significant effect on the critical concentration for tablet disintegration.Conclusion: Determining the type and appropriate amounts of diluent and disintegrant (percolating component) may be useful in the design of tablet formulations.Keywords: Disintegration, Percolation threshold, Croscarmellose sodium, Microcrystalline cellulose, Dibasic calcium phosphate, Pre-gelatinized starc

Development and Optimization of <i>Andrographis paniculata</i> Extract-Loaded Self-Microemulsifying Drug Delivery System Using Experimental Design Model

The objectives of this study were to develop an optimized formulation for an Andrographis paniculata extract (AGPE)-loaded self-microemulsifying drug delivery system (SMEDDS) using an experimental design and evaluate the characteristics of the developed SMEDDS. The solubility of andrographolide (AGP) in various solvents was investigated. The pseudo-ternary phase was constructed to provide an optimal range for each component to form microemulsions (MEs). The formulation was optimized using an I-optimal design mixture type, where the physical stability, droplet size, polydispersity index, and zeta potential were examined. Soft capsules of the optimized AGPE-loaded SMEDDS were manufactured. The dissolution and ex vivo membrane permeation were studied. Oleic acid, Tween® 80, and PEG 400 were the best solubilizers for AGP. The promising surfactant to co-surfactant ratio to generate ME was 3:1. The optimized SMEDDS contained 68.998% Tween® 80, with 13.257% oleic acid and 17.745% PEG 400. The assayed content of AGP, uniformity of dosage unit, and stability complied with the expected specifications. The dissolution and membrane permeability of AGPE-loaded SMEDDS was significantly improved from the A. paniculata extract (p < 0.05). All in all, the developed optimized AGPE-loaded SMEDDS was proven to contain optimal composition and AGP content where a stable ME could spontaneously be formed with enhanced delivery efficacy

Preparation and Application of Carboxymethyl Yam (Dioscorea esculenta) Starch

Yam (Dioscorea esculenta) starch was modified by carboxymethylation. The effect of reaction parameters, amount of sodium hydroxide (NaOH), amount of sodium monochloroacetate (SMCA), and reaction time on the degree of substitution (DS) of carboxymethyl yam starch (CMS), was studied using the Box–Behnken experimental design. Physicochemical and potency to be a tablet disintegrant of CMS were evaluated. CMS with DS in the range of 0.08–0.19 were obtained. The results from regression analysis indicated that the most important factor in controlling DS was the amount of NaOH followed by SMCA content and reaction time. However, high concentration of NaOH and SMCA lowered the DS. The optimal conditions to achieve the highest DS (0.19) were found to be at molar ratios of NaOH and SMCA to anhydroglucose unit of 1.80 and 2.35, respectively, and with the reaction time of 4.8 h. The swelling power and viscosity of CMS increased with an increase in the degree of modification. CMS showed satisfying tablet disintegrant properties. The tablets containing 1.0–4.0 % CMS disintegrated faster than 5 min. Hence carboxymethyl yam starch can be used as an excellent tablet disintegrant in low concentration