Role of sodium l-cysteine alginate conjugate and isopropyl myristate to enhance the permeation enhancing activity of BCS class III drug from TDDS; optimization by central composite design and in vivo pharmacokinetics study

Abstract

Objective

The objective of the present research was to study the effect and optimization of sodium alginate l-cysteine conjugate and permeation enhancer on permeation of high soluble low permeable ropinirole hydrochloride from the transdermal formulation.

Methods

Sodium alginate l-cysteine conjugate was prepared and characterized and the same was added into a transdermal formulation along with IPM as a permeation enhancer. Twelve primary formulations were prepared by solvent casting method and evaluated. The results were fed into Design Expert® Software to obtain optimized formulation. The optimized formulation was evaluated for physicochemical, ex vivo permeation, stability, skin irritation, and pharmacokinetic studies.

Results

The results of the characterization of prepared sodium alginate l-cysteine conjugate confirmed the thiolation process. Stability studies suggested that the drug was compatible with all the excipients. SEM images of the transdermal patch revealed that the amorphous drug was uniformly distributed. From the design space, the optimized formulation from the polymer’s ratio (SA: SACC; 4:6) and IPM 9.5%w/w of polymers weight showed target steady state flux 9.004 µg/cm²/h with maximum drug permeation. The increased target flux and maximum drug permeation from an optimized patch suggested that there was an effect of SACC on ropinirole hydrochloride permeation in the presence of IPM as a permeation enhancer. Pharmacokinetic studies in rabbits showed that the optimized patch improved bioavailability as compared to marketed oral tablets.

Conclusions

The study was concluded that there was a positive effect of sodium alginate l-cysteine conjugate and IPM on ropinirole hydrochloride permeation from the transdermal formulation.

Keywords:

• Design expert
• liquid chromatography–mass spectrometry
• Parkinson’s disease
• proton NMR
• skin irritation studies

Acknowledgments

The authors express thanks to M/s Alembic Pharmaceuticals Ltd, Gujarat, India for providing gift samples of RH pure drug with a certificate of analysis. The authors grateful to Dr. K. P. Channabasavaraja, Principal, Government College of Pharmacy, Karnataka, India for providing required facilities to carry out the experiment and Himalaya Drug Company, Karnataka, India for providing the facility to carry out LC-MS/MS analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).