A comparison of physicochemical properties of high drug-loaded tablets formulated with cold gelatin gummies

Abstract

Stress conditions during formulation affect drug release characteristics of dosage forms. The objective of this study is to formulate high drug-load tablets using minimal heat and water. This study uses paracetamol and calcium carbonate powders, characterized by different thermal and solubility properties, as active pharmaceutical ingredients (APIs), and a combination of nano processing and cold condition in formulating high drug-loaded tablets. A 25.0 % w/v gelatin dispersion was prepared with 3:1 v/v acetic acid : water co-solvent system. The dispersion was stirred while heating to 112 °C for 30 min to produce gummies base that was then left to cool. Two sets of 2.5, 5.0, 7.5 and 10.0 % w/w cold gummies base in API were blended. The blends were dried in microwave drier and characterized using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The blends were processed to granules, evaluated, and tableted. The tablets were evaluated for physicochemical properties. The results were analysed using three group test analysis of co-variance. The FT-IR readings of the blends showed no incompatibility. The DSC thermographs indicated semi-crystalline and amorphous solidifications of paracetamol and calcium carbonate dispersions, respectively. The paracetamol granules exhibited Carrs’ indices < 9.52 %, and Hausner ratios of < 1.11. The calcium carbonate granules gave Carrs’ indices of 20.00-34.38, and Hausner ratios of 1.25-1.52. The paracetamol tablet had tensile strength of > 3.83 MPa, and achieved complete dissolution after 40 min > 81.03 % in comparison with tensile strength of 2.53 – 5.09 MPa, and D₄₀ of 70.11 – 75.75 % of the calcium carbonate tablets. The effect of cold gelatin gummies on high drug-load granules properties was not significant (p> 0.05), but was, on tablet dissolution (p>0.05). Formulating high drug-load tablets with low amount of cold gelatin gummies improved tablet cohesion, crushing strength and dissolution properties, more for low thermal energy and fairly soluble paracetamol than for high thermal energy and poorly soluble calcium carbonate.