Pharmacokinetic Study of a Capsule-based Chronomodulated Drug Delivery System of Salbutamol Sulphate in Rabbits
Purpose: To develop and determine the in vivo performance of a capsule-based pulsatile drug delivery system containing salbutamol sulphate
Methods: A controlled pulsatile release of drug after a programmed 4 h lag period was achieved from cross-linked gelatin capsule shells containing salbutamol pellets, and sealed with a suitable mixture of sodium alginate and ethyl cellulose as plug. In order to confirm the utility of developed system for the management of nocturnal asthma, a crossover study was conducted. six male rabbits were fasted overnight and divided into two groups comprised of 3 rabbits each. The individual rabbits were administered the developed pulsatile capsule and immediate release salbutamol capsule as reference,seeparately. Blood samples were collected from the ear vein of the animals into heparinized tubes and used to determine pharmacokinetic parameters, namely, maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration - time curve (AUC0-‡) using a validated HPLC method.
Results: It was observed that drug release from the optimized time-controlled capsule stopped for a period of approximately 4.25 h with an average Cmax and Tmax of 271.54 } 58.95 ng/ml and 6.00 } 0.25
h. The AUC0-‡ of salbutamol after administration of the time-controlled pulsatile system was 2494.73 } 525.95 ng h/ml while that of the immediate-release formulation was 2352.77 } 432.51 ng h/ml. Using
ANOVA at a significant difference of p < 0.05 (CI 95%), there was no significant difference for the AUC0-‡ between immediate release and the pulsatile capsule developed.
Conclusion: The developed system is capable of releasing salbutamol after a 4 h lag period and can be considered as promising delivery system for time-controlled (pulsatile) delivery of the medication for the management of nocturnal asthma.
Keywords: pH-controlled release, Lag time, Pulsatile release, Hydrocolloid plug, Nocturnal asthma.
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.