DESIGN, IN VITRO AND IN VIVO EVALUATION OF CHRONOMODULATED DELIVERY SYSTEMS OF TERBUTALINE SULPHATE FOR NOCTURNAL ASTHAMA
The present study deals with the design and evaluation of chronomodulated delivery of terbutaline sulphate as a chronotherapeutic approach in the treatment of nocturnal asthma. The basic design is based on the Pulsincap technology and consisted of formaldehyde treated insoluble hard gelatin capsule body filled with glutaraldehyde cross-linked carboxymethyl chitosan microspheres of terbutaline sulphate and sealed with a hydrogel tablet plug. The entire device was enteric coated, so as to prevent the variable gastric emptying time. The glutaraldehyde cross-linked carboxymethyl chitosan microspheres appeared to be roughly spherical with the size range of 4.63Â±0.48 to 11.75Â±0.92Âµm. The prepared microspheres possessed good yield and high encapsulation efficiency. Particle size, encapsulation efficiency and release rate are dependent on the fabrication conditions of the microspheres. Drug release from the microspheres depended on the core: coat ratio, reaction time and the rotational speed used in the preparation of microspheres.Â Formaldehyde treatment efficiently rendered the hard gelatine capsule bodies water insoluble. The ejection of the plug from the chrnomodulated delivery system depended on the nature and concentration of polymer used in the preparation of table plug. A lag time of 3-8hrs was observed for the chronomodulated delivery systems prepared with different hydrogel plugging materials. Among the different polymers studied, HPC showed highest lag time compared to HPMC K4 M and sodium alginate. The Roentgenographic studies revealed the predicted in vivo performance of the developed chronomodulated delivery systems of terbutaline sulphate. Pharmacokinetic analysis revealed the significant increase in tmax, AUC and MRT of optimized chronomodulated system of terbutaline sulphate compared to that of pure drug. The results of the study conclusively proved the suitability of carboxymethyl chitosan microspheres and the adopted Pulsincap technology in the development of chronomodulated delivery systems for terbutaline sulphate in the treatment of nocturnal asthma.
Key words: Nocturnal asthma; Terbutaline sulphate; Chronomodulated systems; Lag time; Roentgenography; In vivo pharmacokinetics
2. Shidhaye SS, Lotlikar VM, Ghule AM, Phutane PK, Kadam VJ. Pulsatile drug delivery systems: an approach for chronotherapeutic diseases. Sys Rev Pharma 2010; 1:55-61.
3. Anil K. Anal, Willem F. Stevens, Carmen RemuËœnÂ´an-LÂ´opez. Ionotropic cross-linked chitosan microspheres for controlled release of ampicillin. Int J Pharm 2006; 312: 166â€“73.
4. Asghar ALF, Chandran S. Multiparticulate formulation approach to colon specific drug delivery: current prosspectives. J Pharm PharmSci 2006;9:327-38.
5. Mourya VK, Inamdara NN, Tiwari A. Carboxymethyl chitosan and its applications. Adv Mat Lett 2010; 1(1): 11-33.
6. Upadhyaya L, Singh J, Agarwal V, Tewari RP. Biomedical applications of carboxymethylchitosans. Carbohydrate Polymers 2013; 91(1):452-66.
7. Masoli M, Fabian M, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy 2004; 59(5): 469â€“78.
8. Mahajan AN, Pancholi SS. Formulation and evaluation of timed delayed capsule device for chronotherapeutic delivery of terbutalinesulphate.Ars Pharm 2010; 50(4): 215-23.
9. Rao NGR, Panchal H, Hadi MA. Formulation and evaluation of biphasic drug delivery system of terbutalinesulphate for chronotherapy.Int J Pharm Bio Sci 2012; 3(3):626 â€“ 37.
10. Emami J, Boushehri MAS, Varshosaz J, Eisaei A. Preparation and characterization of a sustained release buccoadhesive system for delivery of terbutalinesulphate. Research in Pharmaceutical Sciences2013; 8(4): 219-231.
11. Kola R, Ramani ND, Pragatikumar B. Formulation and in-vitro evaluation of terbutalinesulphate sustained release tablets. Indian Journal of Research in Pharmacy and Biotechnology 2013; 1(5): 621-24.
12. Pramodkumar TM, Shivakumar HG. Novel core in cup buccoadhesive systems and films of terbutalinesulphateâ€“development and in vitro evaluation. Asian J Pharm Sci 2006, 1 (3-4): 175-187.
13. Gobade NG, Koland M, Harish KH. Asymmetric membrane osmotic capsules for terbutalinesulphate. Indian J Pharm Sci 2012; 74 (1): 69-72
14. Liu H, Yan H, Zhaoying, Peng K. Preparation of ambroxol hydrochloride carboxymethyl chitosan microspheres without burst release. Afr J Pharm Pharmacol 2011; 5(8): 1063-69.
15. Li GY, Zhong M, Zhou ZD, Ping D, Li YJ. Novel Carboxymethyl Chitosan Microspheres for Controlled Delivery of Chelerythrine. Journal of Macromolecular Science, Part A: Pure and Applied Chemistry 2011;48(11):904-11.
16. Srinatha S, Pandit JK, Singh S. Ionic cross-linked chitosan beads for extended release of ciprofloxacin: in vitro characterization. Indian J Pharm Sci 2008; 70 (1): 16-21.
17. Souto EB, Jose S, PremaMT, Chacko AJ, Thomas AC. Colon specific chitosan microspheres for chronotherapy of chronic stable angina. Colloids and Surfaces B: Biointerfaces 2011; 83: 277â€“83
18. The effect of polymer and CaCl2 concentrations on the sulfasalazine release from alginate-N,Ocarboxymethyl chitosan beads. Farahani EV, Tavakol M, Najafabadi SH. Progress in Biomaterials 2013: 2:10
19. Mastiholimath VS, Dandgi PM, Jain SS, Gadad AP, Kulkarni AR. Time and pH dependent colon specific, pulsatile delivery of theophylline for the treatment of nocturnal asthma. Int J Pharm 2007; 328: 49-56.
20. Bhat A, Chowdary KPR ,Shobharani RH, Narasu L. Chronopharmaceutical release of theophylline from pulsatile capsular device based on programmable erodible plug: influence of various poylmers and plug position. Int J Pharm &Techn2011; 3(1):1419-1432.
21. Tekade AR, Gattani SG. Development and evaluation of pulsatile drug delivery system using novel polymer. Pharm DevTechnol 2009;14(4):380-7.
22. Sharma P, Pathak K. Inulin-Based Tablet in Capsule Device for Variable Multipulse Delivery of Aceclofenac: Optimization and In Vivo Roentgenography. AAPS PharmSciTech 2013; 14( 2): 736-747
23. Gangurde HH, Chordiya MA, Tamizharasi S, SivakumarT. Statistical Optimization of Mesalamine Coated Pellets for Possible Ileoâ€“cecal Targeting. Mahidol University Journal of Pharmaceutical Sciences 2013; 40 (2), 25-44
24. Parauvathanahalli S, Mishra RB. Preparation and in vitro characterization of gellan based floating beads of acetohydroxamic acid for eradication of H. Pylori. Acta Pharm2007; 57: 413â€“427.
25. Nalluri BN, Sunandana B, Sushmitha K. RP-HPLC-PDA Method for the Analysis of Terbutaline sulphate in Bulk, Dosage forms and in Dissolution samples. Journal of Applied Pharmaceutical Science 2013; 3 (03): 126-32.
26. Faiyazuddin MD, Niyaz A, Zeenat I, Talegaonkar S, Bhatnagar A, Khar RK, Ahmad FJ. Development and validation of UHPLC/ESI-Q-TOF-MS method for terbutaline estimations in experimental rodents: stability effects and plasma pharmacokinetics. Curr Pharm Anal 2012; 8(2):1-7.
27. Paget GE, Barnes JM. Toxicity tests. In: Laurence DR, Bacharach AL. Evaluation of drug activities pharmacometrics. 34th ed., vol. I. New York: Academic Press; 1964. p. 134â€“66.
28. Abdelbary A, ELâ€‘Gendy NA, Hosny A. Microencapsulation approach for orally extended delivery of glipizide: in vitro and in vivo evaluation. Indian J Pharm Sci 2012; 74 (4): 319-30
29. Kotadiya R, Patel V, Patel H, Koradiya H. Effect of cross-linking on physicochemical properties of chitosan mucoadhesive microspheres: A factorial approach. Int J Green Pharm 2009: 58-62.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).