DEVELOPMENT AND CHARACTERIZATION OF POLYCAPROLACTONE (PCL)/POLY ((R)-3-HYDROXYBUTYRIC ACID) (PHB) BLEND MICROSPHERES FOR TAMOXIFEN DRUG RELESE STUDIES
Keywords:
Polycaprolactone, Poly (R)-3-Hydroxybutyric acid), Microspheres, SEM, X-RD, Drug releaseAbstract
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.
Â
Downloads
References
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.
Chang RK, Price JC, Whitworth CW. Dissolution characteristics of poly carolactone–polylactide microspheres of chlorpromazine. Drug Dev Ind Pharm 1986;12:2355–80.
Koleske JV. Blends containing polycaprolactone and related polymers. In: DR Paul, S Newman. Eds. Polymer Blends, Academic Press; 1978;2:369–89.
Park TG. Degradation of poly (lactide-coglicolide acid) microspheres: effect of copolymercomposition. Biomaterials 1995;16:1123–30.
Wang DP, Yang MC, Wong CY. Formulation development of oral controlled pellets of diclofenac sodium. Drug Dev Ind Pharm 1997;23:1013-7.
Nokhodchi JF. Microencapsulation of paracetamol by various emulsion techniques using cellulose acetate phthalate. Pharm Tech 2002;26:54-60.
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.
Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine-located poly (ε-caprolactone) microspheres. J Microencapsulation 2005;22:193-03.
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.
Katia P, Seremeta, Chiappetta AD, Alejandro S. Poly (ï¥-caprolactone) Eudragit RS100 and ] Poly(ï¥-caprolactone), Eudragit RS100 Blend submicron particles for the sustained release of the antiretroviral efavirenz. Colloids Surf B 2013;102:441-9.
Huatan, Collett JH, Attwood D, Booth C. Preparation and characterization Poly(ï¥-caprolactone) polymer blends for the delivery of proteins. Biomaterials 1995;16;1297-03.
Balmayor ER, Tuzlakoglu K, Azevedo HS, Reis RL. Preparation and characterization of starch-poly-ï¥-caprolactone micro particles incorporating bioactive agents for drug delivery and tissue engineering applications. Acta Biomater 2009;5:1035-45.
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.
Clarke R, Liu MC, Bouker KB. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 2003;22:7316-39.
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.
Pouton CW, Akhtarb S. Biosynthetic polyhydroxyalkanoates and their potential in drug delivery. Adv Drug Delivery Rev 1996;18:133–62.
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.
Jagadeesh HG, Kusmdevi V. Tamoxifen loaded poly(ï¥ï€caprolactone) based injectable microspheres for breast cancer. Int J Pharm Pharm Sci 2010;2:189-95.
Jordan VC, Murphy CS. Endocrine pharmacologyof antiestrogens as antitumor agents. Endocr Rev 1990;11:49–81.
Furr BJ, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacol Ther 1984;25:127–205.
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.
Jordan VC. Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer. Annu Rev Pharmacol Toxicol 1995;35:195-211.
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.
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.
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.
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.
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.
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.
Chawla SJ, Amiji MM. Biodegradable polycaprolactoe nanoparticles for tumor targeted delivery of tamoxifen. Int J Pharm Pharm Sci 2002;249:127-38.
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.
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.
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.