Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems
Maan Singh,
Harsh Barua,
Vaskuri G. S. Sainaga Jyothi,
Madhukiran R. Dhondale,
Amritha G. Nambiar,
Ashish K. Agrawal,
Pradeep Kumar,
Nalini R. Shastri,
Dinesh Kumar
Affiliations
Maan Singh
Pharmaceutical Solid State Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
Harsh Barua
Solid State Pharmaceutical Cluster (SSPC), Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, Department of Chemical Sciences, University of Limerick, V94T9PX Limerick, Ireland
Vaskuri G. S. Sainaga Jyothi
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad 500037, India
Madhukiran R. Dhondale
Pharmaceutical Solid State Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
Amritha G. Nambiar
Pharmaceutical Solid State Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
Ashish K. Agrawal
Pharmaceutical Solid State Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
Pradeep Kumar
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
Nalini R. Shastri
Solid State Pharmaceutical Research, Hyderabad 500037, India
Dinesh Kumar
Pharmaceutical Solid State Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of cocrystal-based products are currently being marketed and show an upward trend. However, to improve the API properties by cocrystallization, coformer selection plays a paramount role. Selection of suitable coformers not only improves the drug’s physicochemical properties but also improves the therapeutic effectiveness and reduces side effects. Numerous coformers have been used till date to prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are the most commonly used coformers in the currently marketed cocrystal-based products. Carboxylic acid-based coformers are capable of forming the hydrogen bond and contain smaller carbon chain with the APIs. This review summarizes the role of coformers in improving the physicochemical and pharmaceutical properties of APIs, and deeply explains the utility of afore-mentioned coformers in API cocrystal formation. The review concludes with a brief discussion on the patentability and regulatory issues related to pharmaceutical cocrystals.
