Polymers in Medicine

Polim. Med.
Index Copernicus (ICV 2022) – 121.55
MEiN – 70
Average rejection rate – 39.13%
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

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Polymers in Medicine

2018, vol. 48, nr 2, July-December, p. 99–104

doi: 10.17219/pim/105609

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Formulation and solid state characterization of carboxylic acid-based co-crystals of tinidazole: An approach to enhance solubility

Jyotsana R. Madan1,A,B,C,D,E,F, Rishikesh H. Dagade1,B,C,D,F, Rajendra Awasthi2,A,C,D,E,F, Kamal Dua3,A,C,D,E,F

1 Department of Pharmaceutics, Smt. Kashibai Navale College of Pharmacy, Savitribai Phule Pune University, India

2 Amity Institute of Pharmacy, Amity University, Noida, India

3 Discipline of Pharmacy, Graduate School of Health, University of Technology, Sydney, Australia

Abstract

Background. Tinidazole (TNZ) is an anti-parasite drug used in the treatment of a variety of amebic and parasitic infections. It has low solubility in aqueous media and is categorized under Class II of the Biopharmaceutical Classification System.
Objectives. The aim of this research was to study the potential for enhancing the solubility of TNZ using carboxylic acid co-crystals.
Material and Methods. The solubility of TNZ was determined individually using 6 carboxylic acids for forming co-crystals at a 1:1 stoichiometric ratio. Three carboxylic acids – namely tartaric acid (TA), oxalic acid (OA) and glutaric acid (GA) – resulted in the formation of co-crystals with enhanced solubility. An equilibrium solubility study of TNZ co-crystals at 1:1.5 and 1:2 stoichiometric ratios was also carried out. The co-crystals which developed were evaluated using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) to study the drug–co-crystal former interactions.
Results. The solubility of TNZ in distilled water was found to be 0.014 mg/mL. The highest enhancement ratio was obtained with TNZ and TA at a ratio of 1:1. Differential scanning calorimetry thermograms suggested that the drug and carboxylic acids had undergone interactions such as hydrogen bonding. The XRD and DSC results confirmed the formation of co-crystals.
Conclusion. It was concluded that the results of enhanced solubility of TNZ using co-crystals is a clear indication of the potential for co-crystals to be used in the future for other poorly water-soluble drugs, considering that co-crystals are a safe and cost-effective approach.

Key words

solubility, co-crystals, solvent evaporation

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