Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Abstract

New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions H<-0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.

Recent advances in improving oral drug bioavailability by cocrystals

“…The coformers usually are water-soluble molecules such as saccharin, caffeine, nicotinamide, and carboxylic acids. 22 The availability of numerous coformers makes it possible to prepare several cocrystals for each drug and select the most appropriate one. Fig.…”

Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String

“…Molecular complexes, such as inclusion adducts, clathrates, cocrystals and solvates, have been widely used in many fields, including pharmacy [1][2][3][4][5][6], agriculture [7], the food industry [1,8,9] and explosives [10,11]. In the past two decades, cyclodextrins (CDs) have been one of the most extensively studied complexation agents, especially as pharmaceutical excipients [12][13][14][15].…”

“…Quantitative structure-activity relationship (QSPR) methodology has been extensively used for evaluating the formation abilities of molecular complexes, and characterizing their properties [4,[29][30][31][32][33][34][35][36][37][38]. Cyclodextrin binding constant modeling deserves special attention due to its practical importance.…”

Ginsenoside Drug Nanocomposites Prepared by the Aerosol Solvent Extraction System for Enhancing Drug Solubility and Stability

“…Over the past several decades, enormous approaches including polymorphism/morphology control, cocrystals/salts synthesis, inclusion complexes, amorphisation, and co-amorphisation have been explored for the development of high-performance drug formulations aimed at improving the solubilities and dissolution rates of poorly water soluble drugs [ 21 , 22 , 23 , 24 , 25 ]. Recently, micro/nano drug formulations have been produced via combination of micro/nanotechnology and pharmaceutical sciences, which is a most promising strategy for improving the bioavailability of water-insoluble drugs because the high surface area of micro/nano drugs can effectively enhance drug solubility and stability [ 26 ].…”