title: Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach.
abstract: The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies (CAS), Sector 14, Panjab University, Chandigarh, 160 014, India.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Haneef
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies (CAS), Sector 14, Panjab University, Chandigarh, 160 014, India. renukchadha@rediffmail.com.
authors.forename: Renu
authors.initials: R
authors.lastname: Chadha
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D001262:Atenolol / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D003460:Crystallization; D004338:Drug Combinations; D005260:Female; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D000077405:Irbesartan; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D000077333:Telmisartan; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D001262:Atenolol; D000077405:Irbesartan; D000077333:Telmisartan
keywords: coamorphous; cocrystal; eutectic; mechanochemistry; multicomponent solid form