Crystal Structure Transformations and Dissolution Studies of Cimetidine–Piroxicam Coprecipitates and Physical Mixtures

Abstract

Abstract. We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and 52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1. For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially higher dissolution of piroxicam compared to that of drug alone.

The function of oxybuprocaine: aparachuteeffect that sustains the supersaturated state of anhydrous piroxicam crystals

“…S8 and S9 †). [37][38][39][40][41] From these results, it is considered that the parachute effect of OXY against the PX-AH's supersaturated state is not a simple system that interacts 1 : 1, but more intricate interactions among PX, OXY, and water molecules occur. However, since OXY molecules are smaller and simpler than the polymers, we can contribute to the elucidation of the mechanism of the parachute effect on the supersaturated state.…”

Characterization of freeze-dried gallic acid/xyloglucan

“…As mentioned above, GA in 0.2GA/TSX was mostly in an amorphous form but a crystalline form was detected for GA in the 0.4GA/TSX sample. Generally, a drug in an amorphous state will have a higher dissolution than that in a crystalline form 27 . The release of GA from the freeze-dried 0.2GA/TSX is slightly higher than that for the freeze-dried 0.4GA/TSX but not statistically different.…”

Amorphous solid dispersion formation via solvent granulation – A case study with ritonavir and lopinavir

“…Alternatively, it may be due to interference of the nucleation process as inferred in the case of nimodipine:nifedipine co-amorphous blends wherein the T g of the mixture was lower than expected but the system was nevertheless more resistant to crystallization (Knapik-Kowalczuk et al, 2018). However, in terms of dissolution assessment, in many cases, comparisons are made between the co-amorphous system and the corresponding crystalline forms (Dengale et al, 2014, Shayanfar and Jouyban, 2013, Tantishaiyakul et al, 2009). Occasions wherein the dissolution performance is improved relative to that of the pure amorphous drug are usually seen in cases where the amorphous co-former is acidic and the drug is a base, hence salt formation occurs, or the acidic component increases the solubility of the drug by modifying the micro-environmental pH of the solute–solvent interface (Fung et al, 2018).…”