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QSPR Modeling of Biopharmaceutical Properties of Hydroxypropyl Methylcellulose (Cellulose Ethers) Tablets Based on Its Degree of Polymerization

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Abstract

Quantitative structure-property relationship (QSPR) approach has been widely used in predicting physicochemical properties of compounds. However, its application in the estimation of formulation properties based on the polymer used in it to achieve desired formulation characteristics is an extremely challenging process. In the present research, predictive QSPR models were developed by correlating the physicochemical properties of varying grades of cellulose ethers (hydroxypropyl methylcellulose, HPMC) with those of nateglinide (NTG) containing tablets (in vitro and in vivo properties). Sustained release tablets of NTG were prepared by using different grades and concentrations of HPMC and subsequently characterized for in vitro as well as in vivo parameters. Further, QSPR models for individual formulation property were developed by correlating the polymeric physicochemical properties with the formulation characteristics. Subsequently, a true external validation method was used to validate the predictability of developed models. The dissolution study indicated Korsmeyer-Peppas as the best fit model following non-Fickian as drug transport mechanism extending the drug release up to 12 h. In vivo studies showed limited absorption of the NTG. Developed QSPR models showed promising validated predictability for formulation characteristics. The applicability of present work in formulation development could significantly reduce the time and cost expenditure on design trials without actually formulating a delivery system.

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Abbreviations

ADME:

Absorption, Distribution, Metabolism, and Excretion

AUC:

Area Under the Curve

BCS:

Biopharmaceutical Classification System

DSC:

Differential Scanning Calorimetry

ERC:

Elimination Rate Constant

FTIR:

Fourier Transform Infrared

GLZ:

Gliclazide

HCl:

Hydrochloric Acid

HPLC:

High Performance Liquid Chromatography

HPMC:

Hydroxypropyl Methylcellulose

ICH:

International Conference on Harmonization

LOD:

Limit of Detection

LOQ:

Limit of Quantitation

MCC:

Microcrystalline Cellulose

MDS:

Molecular Design Suite

MRT:

Maximum Retention Time

NTG:

Nateglinide

QSPR:

Quantitative Structure-Property Relationship

RMSE:

Root Mean Square Error

RPM:

Rotations Per Minute

t1/2 :

Half-life

USP:

United States Pharmacopeia

VD :

Volume of Distribution

vdW:

van der Waals

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Acknowledgments

The authors are grateful to Ashland Inc. Ltd., Netherlands for providing gift samples of different grades of HPMC (K4M, K15M, K35M, K100M, and K250 PH); Cipla Ltd. (Kurkumbh, Maharashtra, India) for kind gift sample of Nateglinide, Glenmark Pharmaceuticals (Mumbai, Maharashtra, India) for supplying gift sample of Gliclazide; and Colorcon Asia Ltd. (Goa, India) for providing gift samples of microcrystalline cellulose (Avicel PH102), magnesium stearate, and talc.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, PDEA’s Shankarrao Ursal College of Pharmaceutical Sciences and Research Center, Kharadi, Pune, Maharashtra, 411014, India

    Amit J. Kasabe

  2. Department of Pharmaceutics, Satara College of Pharmacy, Satara, Maharashtra, 415004, India

    Ajit S. Kulkarni

  3. Department of Pharmaceutics, BVDU Poona College of Pharmacy, Erandwane, Pune, Maharashtra, 411038, India

    Vinod L. Gaikwad

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  1. Amit J. Kasabe
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Correspondence to Ajit S. Kulkarni.

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This article contained studies with animal subjects performed by the first author and was duly approved by the Institutional Animal Ethics Committee.

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Kasabe, A.J., Kulkarni, A.S. & Gaikwad, V.L. QSPR Modeling of Biopharmaceutical Properties of Hydroxypropyl Methylcellulose (Cellulose Ethers) Tablets Based on Its Degree of Polymerization. AAPS PharmSciTech 20, 308 (2019). https://doi.org/10.1208/s12249-019-1514-9

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