Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

Abstract

In this study molecular modelling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or Flory Huggins interaction parameter in comparison to the molecular modelling approach.The molecular modelling studies predicted successfully the drug-polymer binding energies and the preferable site of interaction between the functional groups. The drug-polymer miscibility and the physical state of bulk materials, physical mixtures and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analysed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drugpolymer functional groups but also the binding strength by estimating the N-coefficientvalues. The findings demonstrate that QM-based molecular modelling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.

RETRACTED ARTICLE: Study of the Transformations of Micro/Nano-crystalline Acetaminophen Polymorphs in Drug-Polymer Binary Mixtures

“…The drug/polymer miscibility was estimated by correlating the energy of mixing from inter-and intra-molecular interactions of the materials used (drug and polymers) (19)…”

Advanced surface chemical analysis of continuously manufactured drug loaded composite pellets

“…Similar to the solubility parameters calculations, it can be claimed via the QM approach that the higher the binding energy the more stable the drug/polymer interactions to develop the solid dispersions in the composites [16].…”

“…The drug molecule was placed within the closeness of the dimeric structure of the polymer to outline the hydrogen bonding followed by the energy optimisation at the B3LYP 6-31G* level. The binding energy was calculated via a single point energies at the M06-2x/6-31G** level [16,21]. The effect of basis set superposition error (BSSE) was corrected by employing counterpoise procedure.…”

“…It has been reported that an optimized dosage form approach can overcome this problem to a certain extent; however, it requires a primeval manufacturing platform [16,17]. It is therefore the purpose of this study to implement a continuous manufacturing HME processing to develop and characterize the composite pellets of a steroid hormone (SH) that can provide e.g.…”

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

“…Since its introduction during the late 1970s, HME has been utilized successfully in manufacturing pharmaceutical products for multiple drug delivery strategies [1][2][3][4][5][6][7][8][9][25][26][27][28]. HME can be adopted as a CM platform by optimizing a suitable set of instrumentations (Figure 1).…”