Journal of the Korea Academia-Industrial cooperation Society (한국산학기술학회논문지)

The Korea Academia-Industrial cooperation Society (한국산학기술학회)
권호 표지
DOI QR코드

DOI QR Code

Development of Gastric Retentive Bi-layered Tablet using Floating Drug Delivery System

부유 기술을 이용한 위체류 이중정의 개발

  • Received : 2015.09.30
  • Accepted : 2015.11.06
  • Published : 2015.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of this study was to develop gastric retentive bi-layered tablet using floating drug delivery technique. Metformin was selected as a model drug due to its narrow absorption window as well as very highly water solubility. These properties of metformin led to be difficult controlling the drug release. The bi-layered tablet was prepared with bi-layered compression machine to minimize interference between floating part and controlling part. The tablet weight, appearance and hardness were evaluated after compression process. The times of 'time to floating' and 'Floating duration' were tested for floating ability and drug release study was also carried out to understand drug release behavior. Furthermore, the drug release of bi-layered tablet was compared with marketed metformin tablet with sustained release pattern (Glucopharge XR$^{(R)}$).The floating ability and drug release behaviors were well controlled by changing amounts of $NaHCO_3$ (floating substance) and hydroxypropyl methylcellulose (HPMC; release control material). Bi-layered tablet had 13s of time to float, over 10h of floating duration and very similar drug release behavior compared with Glucopharge XR$^{(R)}$($f_2$: 89.6). Consequently, the bi-layered tablet with floating ability was successfully prepared and these properties can maximize the efficacy of metformin.

본 이 연구의 목적은 부유 기술을 이용하여 제형이 위에 더 오래도록 머무르면서 약물을 지속적으로 방출하는 이중정을 개발하는 것이다. 실험방법으로는 메트포르민을 주 약물로 선정하였는데, 그 이유는 메트포르민은 주로 소장 상부에서만 흡수되는 좁은 흡수 영역 대를 가지고 있는 점, 용해도가 매우 높아 약물 방출을 조절하는 것이 쉽지 않은 점 등 때문이다. 정제의 부유를 위한 가스를 생성하는 부분과 약물의 방출을 조절하는 부분의 간섭을 최소화하기 위해 이중정 타정 기를 사용해 이중정으로 제조하였으며, 정제의 모양, 질량 및 경도를 측정하였고, 부유정의 중요한 요소인 부유 촉발시간과 부유유지 시간을 평가하였다. 또, 약물의 방출 조절을 평가하기 위해 용출시험을 시행하였으며, 그 결과를 시판되고 있는 메트포르민 서방성 제제인 Glucopharge XR$^{(R)}$과 비교평가 하였다. 그 결과, 부유 촉발제인 $NaHCO_3$ 및 약물 방출 조절제인 hydroxypropyl methylcellulose (HPMC)의 사용량에 따라 13초의 부유 촉발시간, 10시간 이상의 부유 유지시간 및 시판 제제와 매우 유사한 약물 방출 거동을 확인할 수 있었다 ($f_2$: 89.6). 결론적으로 메트포르민을 함유한 위 체류 이중정을 성공적으로 개발할 수 있었으며, 그로 인해 메트포르민의 치료효과도 극대화 할 수 있을 것으로 예상된다.

Keywords

References

  1. M. Rendell, Diabetes "New drug options and old choices", Consultant, Vol. 53, pp. 217-227, 2013.
  2. R. Damodar et al., Preparation and In-vitro Evaluation of Metformin HCl Tablets Containing Sustained Release Beads for Increasing Therapeutic Window. J Bioequivalence & Bioavailability, Vol. 6, pp. 91-95, 2014.
  3. R. Chandrasekaran et al., The influence of calcium ions, acetate and L-glycerate group on the gellan double helix. Carbohydrate Polymer, Vol. 12, pp. 431-442, 1990. DOI: http://dx.doi.org/10.1016/0144-8617(90)90092-7
  4. L. Rojas et al., Metformin: an old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome, Vol. 5, pp. 1-15, 2013. DOI: http://dx.doi.org/10.1186/1758-5996-5-6
  5. H. Balpande et al., Compatibility study of metformin with pharmaceutical excipients. International Journal of ChemTech Research, Vol. 5, pp. 1684-1693, 2013.
  6. G. Namdeo et al., Advances in Gastroretentive Drug Delivery System: An Review, International Journal of Pharmacy and Pharmaceutical Science Research, Vol. 4, pp. 37-48, 2014.
  7. J. Patel et al., Formulation and Optimization of Floating Effervescent Tablet of Roxitidine Acetate, International Journal of Pharmaceutical Archives, Vol. 3, pp. 447-452, 2014.
  8. B. Singh et al., Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention, Journal of Controlled Release, Vol. 63, pp. 235-259, 2000. DOI: http://dx.doi.org/10.1016/S0168-3659(99)00204-7
  9. P. Jha et al., Pharmaceutical Aspects of Various Floating Drug Delivery System, World Journal of Pharmacy and Pharmaceutical Sciences, Vol. 4, pp. 569-589, 2015.
  10. A. Chandel et al., Floating Drug Delivery Systems: A Better Approach, International Current Pharmaceutical Journal, Vol. 1, pp. 110-118, 2012.
  11. Hiten Panchal et al., Novel Approach of Bilayer tablet Technology: An Review. Journal of Pharmaceutical Science and Technology, Vol. 4 (4), pp. 892-904, 2012
  12. Karel Six et al., Clinical study of solid dispersions of itraconazole prepared by hot-stage extrusion, European Journal of Pharmaceutical Sciences, Vol. 24 (2-3), pp. 179-186, 2005. DOI: http://dx.doi.org/10.1016/j.ejps.2004.10.005
  13. Lara Tutunji et al., Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies, Journal of Pharmaceutical and Biomedical Analysis, Vol. 51 (4), pp. 985-990, 2010. DOI: http://dx.doi.org/10.1016/j.jpba.2009.10.023
  14. S. El-Zahabya et al., Design and evaluation of gastroretentive levofloxacin floating mini-tablets-incapsule system for eradication of Helicobacter pylori, Saudi Pharmaceutical Journal, Vol. 22, pp. 570-579, 2014. DOI: http://dx.doi.org/10.1016/j.jsps.2014.02.009
  15. S. Jagdale et al., Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride, AAPS PharmSciTech, Vol. 10, pp. 1071-1079, 2009. DOI: http://dx.doi.org/10.1208/s12249-009-9300-8
  16. S. Alshahrani et al., Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of $Soluplus^{(R)}$ and HPMCAS-HF, AAPS PharmSciTech, Vol. 16, pp. 824-834, 2015. DOI: http://dx.doi.org/10.1208/s12249-014-0269-6
  17. S. Alshehri et al., Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology, Journal of Drug Delivery Science and Technology, Vol. 27, pp. 18-27, 2015. DOI: http://dx.doi.org/10.1016/j.jddst.2015.03.003
  18. G. Rombopoulos et al., Treatment Compliance with Fixed-Dose Combination of Vildagliptin / Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study. International Journal of Endocrinology, Vol. 2015, pp. 1-5, 2015. DOI: http://dx.doi.org/10.1155/2015/251485
  19. T. Yoshida et al., Salting-out taste-masking system generates lag time with subsequent immediate release, International Journal of Pharmaceutics, Vol. 365 (1-2), pp. 81-88, 2009. DOI: http://dx.doi.org/10.1016/j.ijpharm.2008.08.026
  20. S. Banks et al., The influence of substituted phenols on the sol : gel transition of hydroxypropyl methylcellulose (HPMC) aqueous solutions. Carbohydrate Polymers, Vol. 101 (30), pp. 1198-1204, 2014. DOI: http://dx.doi.org/10.1016/j.carbpol.2013.10.061
  21. P. Sharma et al., Co-processing of hydroxypropyl methylcellulose (HPMC) for improved aqueous dispersibility. International Journal of Pharmaceutics, Vol. 485 (1-2), pp. 348-356, 2015. DOI: http://dx.doi.org/10.1016/j.ijpharm.2015.03.036