Diclofenac potassium and isonicotinamide cocrystals for improved solubility: In vitro evaluation of hard capsule formulations

Overview

Diclofenac (DIC), a non-steroidal anti-inflammatory drug, has anti-inflammatory, antipyretic, and analgesic effects. It belongs to the phenylacetic acid class and has various salt forms (such as DIC-Na, and DIC-K). It is a class II drug (low solubility, high permeability) according to the biopharmaceutics classification system. We aimed to prepare the cocrystals (DIC-K+INA cocrystals) by using INA as a coformer to increase the solubility of DIC-K. Powder X-ray Diffraction (PXRD), Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC) analyses were performed. Also, the solubility study was performed in different media (0.1 N HCl pH 1.2, PB pH 4.5, and PB pH 6.8) for pure DIC-K and DIC-K+INA cocrystals. Hard gelatin capsules (DIC-K capsule or DIC-K+INA cocrystal capsule) filled with pure DIC-K or the prepared DIC-K+INA cocrystals after the dry granulation process. A dissolution study for these capsules was conducted in PB pH 6.8. For the DIC-K capsule, the percentage of dissolved DIC-K was 72% at 15 min, while for the DIC-K+INA capsule, the percentage of dissolved DIC-K at 15 min was 92%. In conclusion, the cocrystals have significantly increased the dissolution rate of DIC-K, which would provide a positive contribution to the oral bioavailability of DIC-K.

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1. Esra Demirtürk

1Çukurova University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Adana, Turkey.

0000-0002-8918-0073

2. Gülsüm Gündoğdu

2Turkish-German University, Faculty of Science, Department of Energy Science and Technology, 34820, Beykoz, Istanbul, Turkey.

0000-0003-2380-7942

3. Merve Nenni

3Çukurova University, Faculty  of Pharmacy, Department of Analytical Chemistry, Adana, Turkey.

0000-0003-3165-1060

4. Cem Yamali

4Çukurova University, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Adana, Turkey.

0000-0002-4833-7900

5. Meltem Çetin

5Atatürk University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Erzurum, Turkey.

0000-0002-6414-8309

6. Yılmaz Capan

6Lokman Hekim University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey.

0000-0003-1234-9018

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