DEVELOPMENT AND CHARACTERIZATION OF POLYCAPROLACTONE (PCL)/POLY ((R)-3-HYDROXYBUTYRIC ACID) (PHB) BLEND MICROSPHERES FOR TAMOXIFEN DRUG RELESE STUDIES

  • P. Kumara Babu
  • Y. Maruthi
  • S. Veera Pratap
  • K. Sudhakar
  • Rotimi Sadiku
  • M. N. Prabhakar
  • Jung Il Song
  • M. C. S. Subha
  • K. Chowdoji Rao Department of Polymer Science and Technology Anantapuramu, Andhra Pradesh, India 515003

Abstract

Objective: The objective of this study was to formulate and evaluate the drug release studies using Poly (ε-caprolactone) (PCL)/and Poly (R)-3-hydroxy butyric acid (PHB) blend microspheres for controlled release of Tamoxifen, an anticancer drug.

Methods: Poly (ε-caprolactone), Poly ((R)-3-Hydroxybutyric acid) blend microspheres were prepared through a modified Water/Oil/Water (W/O/W) double emulsion-solvent diffusion method using Dichloromethane as solvent. Tamoxifen (TAM), an anti Cancer drug, was used for encapsulation within PCL/PHB blend microspheres. Morphology, size, encapsulation efficiency and drug release from these microspheres were evaluated by different characterization techniques such as Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry(DSC), Scanning electron microscopy(SEM), X-ray diffraction studies(X-RD) and dissolution test studies respectively.

Results: Drug loaded microspheres were analyzed by FT-IR, which indicates the interaction between drug and polymers. DSC thermograms on drug-loaded microspheres confirmed the polymorphism of Tamoxifen and indicated a molecular level dispersion of drug in the microspheres. SEM confirmed the spherical nature and smooth surface of the microspheres produced. X-RD study was performed to understand the crystalline nature of the drug after encapsulation into the microspheres and confirmed the complete dispersion of the drug in the polymer matrix. In-vitro release studies conducted in different pH which indicated a dependence of release rate on the amount of drug loading and the amount of PCL/PHB, but slow release rates were extended up to 12 h. Kinetic analysis of dissolution data showed a good fit in Peppas equation confirming diffusion controlled drug release.

Conclusions: The research findings obtained from the studies were found to be satisfactory. It can be concluded that biodegradable polymer blend (PCL/PHB) microspheres can be effectively used for preparation of controlled release matrices.

 

Keywords: Polycaprolactone, Poly (R)-3-Hydroxybutyric acid), Microspheres, SEM, X-RD, Drug release

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Author Biographies

Rotimi Sadiku
Department of Polymer Technology
M. N. Prabhakar
Department of Mechanical Engineering
Jung Il Song
Department of Mechanical Engineering

References

1. Sheth M, Kumar RA, Davé RA, Gross SP. Biodegradable polymer blends of poly(lactic acid) and poly(ethylene glycol). J Appl Polym Sci 2000;66:1495–05.
2. Chang RK, Price JC, Whitworth CW. Dissolution characteristics of poly carolactone–polylactide microspheres of chlorpromazine. Drug Dev Ind Pharm 1986;12:2355–80.
3. Koleske JV. Blends containing polycaprolactone and related polymers. In: DR Paul, S Newman. Eds. Polymer Blends, Academic Press; 1978;2:369–89.
4. Park TG. Degradation of poly (lactide-coglicolide acid) microspheres: effect of copolymercomposition. Biomaterials 1995;16:1123–30.
5. Wang DP, Yang MC, Wong CY. Formulation development of oral controlled pellets of diclofenac sodium. Drug Dev Ind Pharm 1997;23:1013-7.
6. Nokhodchi JF. Microencapsulation of paracetamol by various emulsion techniques using cellulose acetate phthalate. Pharm Tech 2002;26:54-60.
7. Nastaran NV, Luginbuehl V, Aboofazeli R, Merkle HP. Preparing Poly (Lactide-co-Glycolic acid) (PLGA) Microspheres containing Lysozyme-zinc precipitate using a double emulsion method. Iran J Pharm Res 2011;10:203-9.
8. Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine-located poly (ε-caprolactone) microspheres. J Microencapsulation 2005;22:193-03.
9. Shen Y, Sun W, Zhu K, Shen Z. Regulation of biodegradability and drug release behavior of aliphatic polyesters by blending. J Biomed Mater Res 2000;50;528-35.
10. Katia P, Seremeta, Chiappetta AD, Alejandro S. Poly (-caprolactone) Eudragit RS100 and ] Poly(-caprolactone), Eudragit RS100 Blend submicron particles for the sustained release of the antiretroviral efavirenz. Colloids Surf B 2013;102:441-9.
11. Huatan, Collett JH, Attwood D, Booth C. Preparation and characterization Poly(-caprolactone) polymer blends for the delivery of proteins. Biomaterials 1995;16;1297-03.
12. Balmayor ER, Tuzlakoglu K, Azevedo HS, Reis RL. Preparation and characterization of starch-poly--caprolactone micro particles incorporating bioactive agents for drug delivery and tissue engineering applications. Acta Biomater 2009;5:1035-45.
13. Sudhakar K, Kumara Babu P, Chandra Babu A, Subha MCS, Chowdoji Rao K. Development of pH sensitive polycaprolactone based microspheres for in-vitro release studies of Triprolidine Hydrochloride. Des Monomers Polym 2014;17:617-23.
14. Clarke R, Liu MC, Bouker KB. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 2003;22:7316-39.
15. Amass W, Tighe B. A review of biodegradable polymers: use, current developments in the synthesis and characterization of biodegradable polyesters, blends of biodegradable polymers and recent advances in biodegradable studies. Polym Int 1998;47:89–144.
16. Pouton CW, Akhtarb S. Biosynthetic polyhydroxyalkanoates and their potential in drug delivery. Adv Drug Delivery Rev 1996;18:133–62.
17. Reis KC, Pereira J, Smith AC, Carvalho CWP, Wellner N, Yakimets. Characterization of polyhydroxybutyrate-hydroxyvalerate (PHB-HV)/maize starch blend films. J Food Eng 2008;89:361–9.
18. Jagadeesh HG, Kusmdevi V. Tamoxifen loaded poly(caprolactone) based injectable microspheres for breast cancer. Int J Pharm Pharm Sci 2010;2:189-95.
19. Jordan VC, Murphy CS. Endocrine pharmacologyof antiestrogens as antitumor agents. Endocr Rev 1990;11:49–81.
20. Furr BJ, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacol Ther 1984;25:127–205.
21. Morrow M, Jordan VC. Risk factors and the prevention of breast cancer with tamoxifen. In: Cancer Surveys: Breast cancer. ed. JT Papademitrio, I Fentiman, Imperial Res. Fund. London: Cold Spring Harbor Lab. Press; 1993;18:211-29.
22. Jordan VC. Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer. Annu Rev Pharmacol Toxicol 1995;35:195-211.
23. Brigger I, Chaminade P, Marsaud V, Appel M, Besnard M, Gurny R, et al. Tamoxifen encapsulation within polyethylene glycol-coated nanospheres, a new anti estrogen formulation. Int J Pharm 2001;214:37-42.
24. Prabhakar MN, Chandra Babu A, Subha MCS, Chowdoji Rao K. Biodegradable graft hydrogel membranes for in-vitro release studies of Leofloxacin Hemihydrate drug. Int J Drug Delivery 2013;5:177-87.
25. Sudhakar P, Madhusudana Rao K, Siraj S, Chandra Babu A, Chowdoji Rao K, et al. Controlled release of hypertensive drug from pH/thermo responsive microbeads. Indian J Adv Chem Sci 2013;2:50-6.
26. Sudhakar K, Madhusudana Rao K, Mallikarjuna B, Prasad CV, Chowdoji Rao K, Subha MCS. Preparation and characterisation of nimesulide loaded poly (methyl methacrulate)/Poly (ethylene oxide) blend microspheres: invitro release studies. Asian J Pharm 2013;7:118-24.
27. Prabhakar MN, Sajankumarji Rao U, Kumara Babu P, Subha MCS, Chowdoji Rao K. Interpenetrating polymer network hydrogel membranes of PLA and SA for control release of Pencillamine drug. Indian J Adv Chem Sci 2013;1:240-9.
28. Rohit RB, Riyaz Ali MO, Padmaja C, Afrasim M. Formulation and evaluation of sustained release dosage form using modified cashew gum. Int J Pharm Pharm Sci 2015;7:141-50.
29. Chawla SJ, Amiji MM. Biodegradable polycaprolactoe nanoparticles for tumor targeted delivery of tamoxifen. Int J Pharm Pharm Sci 2002;249:127-38.
30. Mohanty AK, Guru Prasad M. Dual anti cancer drug loaded methoxy poly ethylene glycol-poly (ε-caprolactone) block copolymeric micelles as novel drug carriers. Int J Pharm Pharm Sci 2014;6:328-32.
31. Korsmeyer RC, Peppas NA. Effect of morphology of hydrophilic polymeric matrices on the diffusion and release of water-soluble drugs. J Membr Sci 1981;9:211-27.
32. Ritger PL, Peppas NA. A simple equation for description of solute release fickian and non-fickian release from non-swellable devices in the form of slabs, Spheres, Cylinders or discs. J Controlled Release 1987;5:23-6.
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Babu, P. K., Y. Maruthi, S. V. Pratap, K. Sudhakar, R. Sadiku, M. N. Prabhakar, J. I. Song, M. C. S. Subha, and K. C. Rao. “DEVELOPMENT AND CHARACTERIZATION OF POLYCAPROLACTONE (PCL)/POLY ((R)-3-HYDROXYBUTYRIC ACID) (PHB) BLEND MICROSPHERES FOR TAMOXIFEN DRUG RELESE STUDIES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 9, July 2015, pp. 95-100, https://innovareacademics.in/journals/index.php/ijpps/article/view/7058.
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