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AAPS PharmSciTech

, 20:308 | Cite as

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

  • Amit J. Kasabe
  • Ajit S. KulkarniEmail author
  • Vinod L. Gaikwad
Research Article
  • 5 Downloads

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.

KEY WORDS

QSPR modeling biopharmaceutical degree of polymerization HPMC in vivo 

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

Notes

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.

Compliance with Ethical Standards

Authors declare that the experiments are in compliance with the current laws of India.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Standards

Authors declare that the experiments comply with the current laws of India.

Statement of Human and Animal Rights

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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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Amit J. Kasabe
    • 1
  • Ajit S. Kulkarni
    • 2
    Email author
  • Vinod L. Gaikwad
    • 3
  1. 1.Department of Pharmaceutical Chemistry, PDEA’s Shankarrao Ursal College of Pharmaceutical Sciences and Research CenterPuneIndia
  2. 2.Department of Pharmaceutics, Satara College of PharmacySataraIndia
  3. 3.Department of Pharmaceutics, BVDU Poona College of PharmacyPuneIndia

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