Ilma Nugrahani

Zwitterionic cocrystal of diclofenac and l-proline: Structure determination, solubility, kinetics of cocrystallization, and stability study

&NA; In recent decades, the design of cocrystals has developed significantly due to the unique characteristics and advantages of cocrystals, which help to improve the physicochemical properties of drugs, especially solubility. Zwitterions are attractive and interesting co‐formers. However, the physicochemical properties of cocrystals with zwitterionic co‐formers, i.e. zwitterionic cocrystals, have not been adequately evaluated. In this study, solid‐state characterization of a newly developed zwitterionic cocrystal of diclofenac (DFA), a non‐steroidal anti‐inflammatory drug, and the amino acid l‐proline (PRO) was performed using Fourier‐transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction (PXRD) analyses. In addition, the crystal structure of the cocrystal (DFA‐PRO) was determined by single‐crystal X‐ray diffraction analysis, after which the zwitterionic structure was confirmed. The cocrystallization during co‐grinding, which was investigated by PXRD, followed first‐order kinetics. Furthermore, the solubility of the zwitterionic cocrystals was 7.5‐times higher than that of the DFA crystals. The results indicate that the cocrystal is stable under ambient conditions; however, it hydrates and transforms into a mixture of l‐proline monohydrate crystals and DFA crystals under conditions of high humidity. Graphical abstract Figure. No caption available.

HYDRATE TRANSFORMATION STUDY OF FLUOROQUINOLONE ANTIBIOTICS USING FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR)

Objective: There are many successful products on the market which are the culmination of the self-micro-emulsification lipid technology applications. Despite the importance of lipid-based formulations, these systems have some limitations including; stability, complexity during large scale manufacturing process and limited dosage forms to such as soft gelatin capsule. In order to overcome these limitations, the prospect of converting self-micro-emulsifying drug delivery systems (SMEDDS) into tablet dosage form was investigated in this study. Methods: A self-micro-emulsifying oil formulation representing type III A lipid class composed of glycerox 767HC/croduret 40 ss at ratios of (80/20) was converted into solid SMEDDS using solid carrier adsorption method. Powder blends containing magnesium trisilicate hydrate (MTSH) or magnesium lluminum silicate (MAS) at various oil loading factors were mixed with MCC with and without various binders and compressed into tablets using a fixed loading force of approximately of 5 KN. Hardness profiles of these oil loaded tablets were then analyzed. Results: Powder compacts which contained MTSH with and without SMEDDS oil had shown relatively better compaction properties than MAS. Adding SMEDDS oil solution to either MTSH or MAS at ratios of 1:9 has relatively reduced tablets hardness by almost 2 or 4 folds, respectively. Conclusion: Progressive inclusion of increasing amounts of SMEDDS oil solution adsorbed unto the solid carrier has incurred a further reduction in the hardness of SMEDDS tablets. It appears that manufacturing of tablet SMEDDS can only be attainable for highly potent drugs as minimal amounts of oil solution added to the powder blends can adversely affect the mechanical strength of compressed tablet.

Formation and Characterization of Mefenamic acid-Nicotinamide Cocrystal during Co-milling Based on X-ray Powder Diffraction Analysis -

Article history: Received on: 11/05/2016 Revised on: 30/06/2016 Accepted on: 16/08/2016 Available online: 29/10/2016 Mefenamic acid (MFA) and Nicotinamide (NIC) cocrystal formation in co-milling treatment was investigated by x-ray powder diffractometry (XRPD). Two polymorphic form of Mefenamic acid (MFA form I and MFA form II) were used to form a cocrystal with nicotinamide. Co-milling treatment was carried out at room temperature in a 1:2 molar ratio of MFA and NIC for various times up to 60 min. Samples were analyzed by XRPD. The XRPD showed that MFA form I and MFA form II formed cocrystal with NIC in the same diffractograms pattern. There was no intermediate amorphous form during milling process. The cocrystal formation mechanism was predicted via intermediate eutectic mixtures. The cocrystal formation from MFA form II (15 min) was faster than from MFA form I (45 min) which may explained by variations unit cell dimensions of MFA form I and MFA form II and also the polymorphic transformation of MFA form I.

Development and Validation of Content Uniformity Analytical Procedure of Glipizide Extended Release Tablet

Glipizide is an oral anti-diabetic drug which belongs to the class of second-generation sulfonyl-ureas. The matrices of an extended release (ER) dosage form often bring some problems in the analytical work, so it needs suitable procedure for extraction and separation. In this experiment, the glipizide ERs were prepared for a quantitative analysis by solid phase extraction (SPE) using HLB sorbent and dissolved in the mobile phase. Next, the sample preparations were analyzed with a Reversed Phase High-Performance Liquid Chromatography (RP-HPLC). The good separation was achieved on an HPLC YMC Triart C18 (150 x 4.6 mm, ID S-5 µm 12nm) column. The 0.1M buffer sodium dihydrogen phosphate mono base pH 6.00 ± 0.05 - methanol in the ratio 55:45 was used as the mobile phase, with flow rate of 1.0 mL/min, and column temperature was maintained at 30oC. The eluted compound was monitored at a wavelength of 225 nm using an UV detector, within a run time of 23 min. Analytical procedure development yielded a good linearity at a range concentration 0.01 – 0.07 mg/mL with its calibration curve: y = 58985.35x + 13.88 and the correlation coefficient of r = 0.9995. The limit of detection (LOD) was determined as 0.0025 mg/mL, meanwhile the limit of quantitation (LOQ) was 0.0075 mg/mL. The % RSD the inter-day precision was obtained 0.90%, 1.40% and 0.86%, while the % RSD the intra-day precision was obtained 1.23%. The mean recovery of glipizide placebo spike was 100.68%. It was concluded that the procedure is valid and can be applied for determination content uniformity of glipizide in the ER tablet dosage forms.

The Cold Contact Method as a Simple Drug Interaction Detection System

The physical interaction between 2 substances frequently occurs along the mixing and manufacturing of solid drug dosage forms. The physical interaction is generally based on coarrangement of crystal lattice of drug combination. The cold contact method has been developed as a simple technique to detect physical interaction between 2 drugs. This method is performed by observing new habits of cocrystal that appear on contact area of crystallization by polarization microscope and characterize this cocrystal behavior by melting point determination. Has been evaluated by DSC, this method is proved suitable to identify eutecticum interaction of pseudoephedrine HCl-acetaminophen, peritecticum interaction of methampyrone-phenylbutazon, and solid solution interaction of amoxicillin-clavulanate, respectively.