Characterization of Meloxicam and Malonic Acid Cocrystal Prepared With Slurry Method

Abstract

<em>Meloxicam (MLX) is a nonsteroidal anti-inflammatory drugs (NSAID) which belong to Biopharmaceutical Classification System (BCS) class II, which have a low solubility level with a high permeability. Therefore, to enchance is solubility level, physical modification of the meloxicam is required. It can be done by the cocrystal formation. Cocrystal contained active ingredients and coformer which bind through the hydrogen bond. This study used malonic acid (MA), since it contained carboxylic group which expected to form hydrogen bonds. Slurry is a method of cocrystal formation by mixing two ingredients, i.e. active ingredients of the drugs and its cofomer, dissolved in a solvent and may be formed due to the heat energy released by the friction between particles and their crusher. This study aimed to determine the characteristic of meloxicam-malonid acid cocrystal by 1:1 mol ratio using PXRD, DSC and FTIR. The result of PXRD charaterization indicated a new peak at angle 9,4° and 18,5°. The result of DSC characterization indicated an endothermic peak with a low melting point at 97,64°C ; 152,62°C ; 176,87°C temperature. The result of FTIR characterization indicated a shirt of the O-H uptake band from at wave number 3126-2980 cm<sup>-1</sup> to 3292-2951 cm<sup>-1</sup>, the N-H uptake band of meloxicam at wave number 3492 cm<sup>-1</sup> to 3525 cm<sup>-1</sup></em>

Technique Development in Improving the Solubility of Poorly Water Soluble Drugs (BCS II and IV): a Review Study

“…Sharp peaks on the diffractogram show that the two compounds between the Active Pharmaceutical Ingredients (API) and coformers include cocrystals. New peaks formed on the cocrystals signal the formation of the cocrystal phase and the molecular interaction between the two materials to form cocrystals (Najih et al, 2018). Figure 1 illustrates the diffractogram pattern of pure piperine, which has prominent and sharp diffraction peaks at 2, namely 14.…”

“…To identify cocrystal formation, an exothermic peak must be followed by an endothermic peak or the melting point alteration of the DSC thermogram. In more than 50% of situations the cocrystal's melting point is lower than the melting point of each active component and coformer or between the melting points of the active ingredient and coformer (Najih et al, 2018). Pure carvedilol and cocrystal formulations utilizing succinic acid, fumaric acid, and oxalic acid exhibited sharp endothermic peaks at 119.5°C, 94°C, 115°C, and 100.5°C, respectively, on DSC thermograms.…”

“…Hydrogen bonding is one of the connections that contribute to creating cocrystals, and this interaction can be identified via peaks in the infrared spectrum. In the infrared spectrum, the development of cocrystals can result in peak shifts, a drop in peak intensity, or the appearance of additional peaks (Najih et al, 2018). Figure 2…”

Binary Mixtures of Meloxicam and L-Tartaric Acid for Oral Bioavailability Modulation of Pharmaceutical Dosage Forms

“…In the literature, various meloxicam co-crystals have been reported with various carboxylic acids: 1-hydroxy-2-naphthoic acid, glutaric acid, L-malic acid, salicylic acid, fumaric acid, succinic acid, maleic acid, malonic acid, gentisic acid, 4-hydroxybenzoic, acid, adipic acid, (þ)-camphoric acid, glycolic acid, benzoic acid, DL-malic acid, hydro-cinnamic acid, ascorbic acid, acetyl salicylic acid [11,[14][15][16][17][18][19][20][21][22][23] and hydrosulphate monohydrate [21]. The physical chemical characterization methods of meloxicam mixtures were as follows: differential scanning calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), complemented by solubility, in vitro release and stability studies [6,8].…”