Abstract
The quantitative structure–activity relationship (QSPR) model was formulated to quantify values of the binding constant (lnK) of a series of ligands to beta–cyclodextrin (β-CD). For this purpose, the multivariate adaptive regression splines (MARSplines) methodology was adopted with molecular descriptors derived from the simplified molecular input line entry specification (SMILES) strings. This approach allows discovery of regression equations consisting of new non-linear components (basis functions) being combinations of molecular descriptors. The model was subjected to the standard internal and external validation procedures, which indicated its high predictive power. The appearance of polarity-related descriptors, such as XlogP, confirms the hydrophobic nature of the cyclodextrin cavity. The model can be used for predicting the affinity of new ligands to β-CD. However, a non-standard application was also proposed for classification into Biopharmaceutical Classification System (BCS) drug types. It was found that a single parameter, which is the estimated value of lnK, is sufficient to distinguish highly permeable drugs (BCS class I and II) from low permeable ones (BCS class II and IV). In general, it was found that drugs of the former group exhibit higher affinity to β-CD then the latter group (class III and IV).
Highlights
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]
It was found that a single parameter, which is the estimated value of lnK, is sufficient to distinguish highly permeable drugs (BCS class I and II) from low permeable ones (BCS class II and IV)
The most commonly used compounds in pharmaceutical formulations belonging to this class are alpha- (α-CD), beta- (β-CD), gamma- (γ-CD) cyclodextrins and their analogues such as
Summary
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]. 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]. 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]. The main criterion used for distinguishing different CDs (α-CD, β-CD and γ-CD) corresponds to six, seven and eight D-glucopyranose units, respectively. These excipients have been used for all main types of drug delivery systems (oral, nasal, rectal, dermal, ocular, parenteral) [13,21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
