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

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 

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

D Dahlgren and H Lennernäs. Intestinal permeability and drug absorption: Predictive experimental, computational and in vivo approaches. Pharmaceutics 2019; 11, 411.

B Shekhawat P and VB Pokharkar. Understanding peroral absorption: Regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta. Pharm. Sin. B 2017; 7, 260-80.

VK Mourya and NN Inamdar. Trimethyl chitosan and its applications in drug delivery. J. Mater. Sci. Mater. Med. 2009; 20, 1057-79.

TMM Ways, WML Lau and VV Khutoryanskiy. Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers 2018; 10, 1-37.

AF Kotzé, HL Luessen, BJ de Leeuw, BG de Boer, JC Verhoef and HE Junginger. N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: In vitro evaluation in intestinal epithelial cells (Caco-2). Pharm. Res.1997; 14, 1197-202.

JH Hamman, CM Schultz and AF Kotzé. N-Trimethyl chitosan chloride: Optimum degree of quaternization for drug absorption enhancement across epithelial cells. Drug. Dev. Ind. Pharm. 2003; 29, 161-72.

AF Kotzé, HL Leußen, AG de Boer, JC Verhoef and HE Junginger. Chitosan for enhanced intestinal permeability: prospects for derivatives soluble in neutral and basic environments. Eur. J. Pharm. Sci. 1999; 7, 145-51.

W Wang, Q Meng, Q Li, J Liu, M Zhou, Z Jin and K Zhao. Chitosan derivatives and their application in biomedicine. Int. J. Mol. Sci. 2020; 21, 487.

MM Thanou, AF Kotzé, T Scharringhausen, HL Luessen, AG de Boer, JC Verhoef and HE Junginger. Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal caco-2 cell monolayers. J. Control. Release. 2000; 64, 15-25.

MS Arayne, N Sultana, FA Siddiqui. Determination and quantification of cetirizine HCl in dosage formulations by RP-HPLC. Pak. J. Pharm. Sci. 2005; 18, 7-11.

P Katewongsa, K Terada and T Phaechamud. Spatial distributing lubricants from Raman mapping and scanning electron microscopy-energy dispersive X-ray spectroscopy on cetirizine dihydrochloride fast disintegrating tablet properties. J. Pharm. Investig. 2017; 47, 249-62.

APG Nikalje, R Gadikar and S Turwale. A simple stability indicating HPLC method for simultaneous determination of levocetirizine dihydrochloride, phenylephrine hydrochloride and paracetamol in pharmaceuticals. Int. J. Pharm. Sci. Res. 2019; 10, 2497-503.

C Chen. Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine. Curr. Med. Chem. 2008; 15, 2173-91.

LA Samuels. Pharmacotherapy update: Hyoscine butylbromide in the treatment of abdominal spasms. Clin. Med. Ther. 2009; 1, 647-55.

AA Gouda. Kinetic spectrophotometric determination of hyoscine butylbromide in pure form and in pharmaceutical formulations. Arab. J. Chem. 2010; 3, 33-8.

B Shekhawat P and BV Pokharkar. Understanding peroral absorption: Regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta Pharm. Sin. B 2017; 7, 260-80.

W Boonyo, HE Junginger, N Waranuch, A Polnok and T Pitaksuteepong. Chitosan and trimethyl chitosan chloride (TMC) as adjuvants for inducing immune responses to ovalbumin in mice following nasal administration. J. Control. Release 2007; 121, 168-75.

W Boonyo. 2010, Effect of the degree of quaternization and molecular weight of trimethyl chitosan for enhancing the immune responses after nasal vaccination. Ph. D. Dissertation. Naresuan University, Phitsanulok, Thailand.

The United State Pharmacopeial Convention. The United States pharmacopeia 2018: USP 41; The national formulary: NF 36. United Book Press, Maryland, 2018.

I Brondz, A Brondz. British Pharmacopoeia. Vol. I-III. Her Majesty’s Stationery Office (HMSO), London, 2015.

M Masuelli. Mark-Houwink parameters for aqueous-soluble polymers and biopolymers at various temperatures. J. Polym. Biopolym. Phys. Chem. 2014; 2, 37-43.

S Boontha, HE Junginger, N Waranuch, A Polnok and T Pitaksuteepong. Formation of particles prepared using chitosan and their trimethyl chitosan derivatives for oral vaccine delivery: Effect of molecular weight and degree of quaternization. Songklanakarin J. Sci. Technol. 2010; 32, 363-71.

SB Kiran, SD Ravindra, C Bhaskar, P Anant and SK Shivajirao. Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices. AAPS PharmSciTech 2007; 8, E1-E9.

O Phongwarin, P Wongchan-udom, P Rewsuwan, W Boonyo, S Boontha and T Pitaksuteepong. Influence of trimethyl chitosan on dissolution of charged drugs from oral solid dosage forms. J. Interdiscipl. Network. 2013; 2, 65-70.

Downloads

Published

2021-05-14

How to Cite

BOONTHA, S. ., JAICHUM, D. ., KUNSEANG, K. ., WANJAI, K. ., BOONYO, W. ., & PITAKSUTEEPONG, T. . (2021). Effect of Trimethyl Chitosan with Different Degrees of Quaternization on the Properties of Tablets Prepared using Charged Model Drugs. Walailak Journal of Science and Technology (WJST), 18(10), Article 9880 (10 pages). https://doi.org/10.48048/wjst.2021.9880