Fabrication of Tizanidine Loaded Patches Using Flaxseed Oil and Coriander Oil as a Penetration Enhancer for Transdermal Delivery.

Muhammad Akhlaq,Mahendran Sekar,Mireia Mallandrich Miret,Shivkanya Fuloria,Vetriselvan Subramaniyan,Asif Nawaz,Neeraj Kumar Fuloria,Kathiresan V Sathasivam,Muhammad Safdar,Abul Kalam Azad,Sajid Raza,Yuan Seng Wu,Dhanalekshmi Unnikrishnan Meenakshi

doi:10.3390/polym13234217

Abstract

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs.

Highlights

Transdermal drug delivery systems (TDDSs) are self sufficient, separate dosage forms that are called patches [1]
RL100, ethyl cellulose (99%), polyvinyl alcohol-1750 (PVA1750), polyvinyl pyrrolidoneK30 (PVAK30), low average molecular weight chitosan (100,000 g/mol) with degree of deacetylation (75–85%) and viscosity of 20–300 cP and di-n-butylphthalate were purchased from Sigma-Aldrich
The maximum drug release was observed for the formulation having a chitosan/thiolated chitosan polymer ratio of 0.3:1.7, ethyl cellulose (EC)/PVP ratio of 1:5, and Eudragit RL100/PVP ratio of 1:5

Summary

Introduction

Transdermal drug delivery systems (TDDSs) are self sufficient, separate dosage forms that are called patches [1]. Hydrophobic polymers (e.g., ethyl cellulose) have excellent film-forming properties and are considered nonirritating, nonallergenic, and nontoxic polymers. These polymers delay the release of the drug from the matrix, due to their low water permeability. Penetration enhancers have polar and nonpolar molecules that act by modifying the multilamellate pathway for penetration and even increasing the diffusivity of drugs across skin proteins [5]. This has encouraged investigators to discover pathways using various types of enhancers to overcome the obstacles of the skin [6]. It is very important to render exploration of penetration enhancers from natural sources that exhibit no toxicity

Objectives

Methods

Results

Discussion

Conclusion