Effect of Trimethyl Chitosan with Different Degrees of Quaternization on the Properties of Tablets Prepared using Charged Model Drugs

Supavadee  BOONTHA; Duangdau  JAICHUM; Kannikar  KUNSEANG; Korrakrit  WANJAI; Worawan  BOONYO; Tasana  PITAKSUTEEPONG

doi:10.48048/wjst.2021.9880

Authors

Supavadee BOONTHA School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand https://orcid.org/0000-0003-3335-6081
Duangdau JAICHUM School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand
Kannikar KUNSEANG School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand
Korrakrit WANJAI School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand
Worawan BOONYO Department of Technical Pharmacy Program, Sirindhorn Collage of Public Health Phitsanulok, Phitsanulok 65130, Thailand https://orcid.org/0000-0003-0961-1724
Tasana PITAKSUTEEPONG Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand https://orcid.org/0000-0001-5641-5430

DOI:

https://doi.org/10.48048/wjst.2021.9880

Keywords:

Absorption enhancers, Cetirizine dihydrochloride, Dissolution profiles, Hyoscine butylbromide, Intrinsic viscosity

Abstract

Trimethyl chitosan (TMC) has demonstrated effectiveness as an absorption enhancer for hydrophilic and high molecular weight (MW) drugs across the intestinal epithelium. However, the effects of degrees of quaternization (DQ) of TMC on the absorption of negatively and positively charged drugs have not been investigated. This investigation aimed to determine the properties of the tablets formulated using TMC with different DQ. In this study, TMC with DQ of 20 % (TMC-20), 40 % (TMC-40) and 60 % (TMC-60) were synthesized and subsequently characterized. Cetirizine dihydrochloride (CHC) and hyoscine butylbromide (HBB) were used as negatively and positively charged model drugs. Eight tablet formulations were prepared using the wet granulation method. The formulated tablets were evaluated regarding their properties in terms of thickness and hardness, weight variation, disintegration time, and dissolution profile. These tablets were evaluated according to the standards set by the United States Pharmacopeia (USP41) guidelines. The results showed that TMC with all DQ have the MW and an intrinsic viscosity less than starting chitosan. The MW and an intrinsic viscosity of the synthesized TMC decreased with increasing DQ. In order to evaluate the effect of TMC with various DQ on the properties of the formulated tablets, all tablet formulations prepared had good characteristics and were found to be within the acceptable range based on the requirements of USP. In conclusion, TMC had a minor retarding effect on the dissolution profiles of CHC from the formulated tablets. Still, TMC was able to significantly delay the release of HBB from the formulated tablets (p > 0.05). When TMC with various DQ were compared, TMC-60 showed higher drug release than TMC-20 and TMC-40. In our study, we observed a possible interaction between the model drugs and TMC. This warrants the need for further studies.

HIGHLIGHTS

Degree of quaternization represents the charge density of trimethyl chitosan (TMC)
Degradation of the polymer backbone occurred in the synthesis reaction step
TMC affects dissolution profiles of a negative charged drug
Ionic interaction and viscous gel layer of TMC affects the model drug release

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