Search results for: coformer

Authors: Akshita Jindal, Renu Chadha, Maninder Karan

Abstract:

Supramolecular chemistry has gained recent eminence in a flurry of research documents demonstrating the formation of new crystalline forms with potentially advantageous characteristics. Mesalamine (5-amino salicylic acid) belongs to anti-inflammatory class of drugs, is used to treat ulcerative colitis and Crohn’s disease. Unfortunately, mesalamine suffer from poor solubility and therefore very low bioavailability. This work is focused on preparation and characterization of cocrystal of mesalamine with nicotinamide (MNIC) a coformer of GRAS status. Cocrystallisation was achieved by solvent drop grinding in stoichiometric ratio of 1:1 using acetonitrile as solvent and was characterized by various techniques including DSC (Differential Scanning Calorimetry), PXRD (X-ray Powder Diffraction), and FTIR (Fourier Transform Infrared Spectrometer). The co-crystal depicted single endothermic transitions (254°C) which were different from the melting peaks of both drug (288°C) and coformer (128°C) indicating the formation of a new solid phase. Different XRPD patterns and FTIR spectrums for the co-crystals from those of individual components confirms the formation of new phase. Enhancement in apparent solubility study and intrinsic dissolution study showed effectiveness of this cocrystal. Further improvement in pharmacokinetic profile has also been observed with 2 folds increase in bioavailability. To conclude, our results show that application of nicotinamide as a coformer is a viable approach towards the preparation of cocrystals of potential drug molecule having limited solubility.

Keywords: cocrystal, mesalamine, nicotinamide, solvent drop grinding

Procedia PDF Downloads 133

Authors: B. S. Muddukrishna, Karthik Aithal, Aravind Pai

Abstract:

Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.

Keywords: dynamic solubility, Etraverine, in vitro dissolution, slurry method

Procedia PDF Downloads 307

Authors: Maninderjeet K. Grewal, Sakshi Bhatnor, Renu Chadha

Abstract:

The composition of pharmaceutical entities and the molecular interactions can be altered to optimize drug properties such as solubility and bioavailability by the crystal engineering technique. The present work has emphasized on the preparation, characterization, and biopharmaceutical evaluation of co-crystal of BCS Class II anti-osteoarthritis drug, Oxaprozin (OXA) with aspartic acid (ASPA) as co-former. The co-crystals were prepared through the mechanochemical solvent drop grinding method. Characterization of the prepared co-crystal (OXA-ASPA) was done by using analytical tools such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermogram of OXA-ASPA cocrystal showed a single sharp melting endotherm at 235 ºC, which was between the melting peaks of the drug and the counter molecules suggesting the formation of a new phase which is a co-crystal that was further confirmed by using other analytical techniques. FT-IR analysis of OXA-ASPA cocrystal showed a shift in a hydroxyl, carbonyl, and amine peaks as compared to pure drugs indicating all these functional groups are participating in cocrystal formation. The appearance of new peaks in the PXRD pattern of cocrystals in comparison to individual components showed that a new crystalline entity has been formed. The Crystal structure of cocrystal was determined using material studio software (Biovia) from PXRD. The equilibrium solubility study of OXA-ASPA showed improvement in solubility as compared to pure drug. Therefore, it was envisioned to prepare the co-crystal of oxaprozin with a suitable conformer to modulate its physiochemical properties and consequently, the biopharmaceutical parameters.

Keywords: cocrystals, coformer, oxaprozin, solubility

Procedia PDF Downloads 81