OPTIMIZATION AND CHARACTERIZATION OF PEG-PCL-PEG TRIBLOCK COPOLYMER AS CARRIER OF DRUG USING FULL FACTORIAL DESIGN

Objective: Triblock copolymer of poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) was applicated as hydrophobic drug. This study aims to optimization and characterization of PECE triblock copolymer as carriers of hydrophobic drug (ketoprofen). Methods: Triblock copolymer of PECE was prepared with varying composition ratio of PEG and PCL by ring-opening and coupling reaction. The characteristics of triblock copolymer were characterized using FTIR and DSC. Variation composition ratio of poly(ɛ-caprolactone) (PCL)/poly(ethylene glycol) (PEG) and ratio PECE/drug as factors for optimization using full factorial design. Ketoprofen was loaded into PECE triblock copolymer micelles by emulsification and solvent evaporation method. Responses were measured particle size, entrapment efficiency (EE) and drug solubility. Results: The result of this study showed that a higher ratio of PCL/PEG and ratio of PECE/drug, reducing particle size, increasing EE and improving drug solubility. The optimum formula obtained by ratio of PCL/PEG is 2:1 and ratio of PECE/drug is 40:1 with particle size is 356,967±9,142 nm, EE is 57,751±0,437%, drug solubility is 32,648±0,200 µg/ml and zeta potential-18,867±2,578 mV. A full factorial design was applied to determine the optimum formula for the PECE triblock copolymer as drug carriers. Conclusion: The PECE triblock copolymer was preparated using ring-opening polymerization method with Sn(Oct)2 as a catalyst and then continued the reaction with HMDI as coupling agent. Ketoprofen was loaded into PECE triblock copolymer using methods emulsification and solvent evaporation

METHOD VALIDATION OF SIMVASTATIN IN PCL-PEG-PCL TRIBLOCK COPOLYMER MICELLES USING UV-VIS SPECTROPHOTOMETRIC FOR SOLUBILITY ENHANCEMENT ASSAY

Objective: This study aims to increase the solubility of simvastatin (SIM), a hydrophobic drug, by incorporating it into PCL-PEG-PCL triblock copolymer micelles and validating the assay method used, namely Uv-Vis spectrophotometric. Methods: The shake flask method was used to determine the increase in solubility experienced by SIM after being incorporated into the micellar system. The values ​​of maximum wavelength (λmax), linearity, LOD, LOQ, accuracy, and precision were used as parameters measured to assess the validity of the assay method used. Results: The results showed that PCL-PEG-PCL triblock copolymer micelles could increase SIM solubility by 9.7 times (89.49±5.75 µg/ml) compared to SIM without modification (9.19±0.24 µg/ml). The validation results show the λmax value of 239 nm, a linear calibration curve with an R-value of 0.9994, LOD and LOQ of 0.33 µg/ml and 1.00 µg/ml, accurate measurement with recovery at concentrations of 80%, 100%, and 120% were 102.93±1.32%, 100.78±0.40%, and 104.58±0.79% and also had good precision ​​with RSD<2%. Conclusion: The PCL-PEG-PCL triblock copolymer micelles can increase SIM solubility and the Uv-Vis spectrophotometric method has been validated successfully for the quantitative analysis of SIM in PCL-PEG-PCL triblock copolymer micelles

Optimasi Formula Tablet Lepas Lambat Mucoadhesive Nifedipin dengan Carbopol 940 dan HPMC K15M Sebagai Matriks secara Simplex Lattice Design

Nifedipin is a calcium chanel blocker has been used for hypertension treatment. Nifedipin has a short half-life (2-4 hours), and perfectly absorb in stomach. These characteristics indicate a good candidate for mucoadhesive formulation. This research aimed to optimize and determine the influence of the Carbopol 940 and HPMC K15M proportion on the physical properties of the tablet and the drug release. Tablets preparation using dry granulation method was carried out using difference proportion of HPMC K15M (A) and Carbopol 940 (B) for each formula i.e. 0% A: 100% B 940, 25% A: 75% B, 50% A: 50% B, 75% A: 25% B and 100% A: 0% B. The weighting of each tablet 250 mg with nifedipin 20 mg per tablet. Mucoadhesive strength was determined using rabbit gastric and the drug release using buffer chloride addition by 0.5% sodium lauryl sulfate pH 1.2 for 6 hours. Optimum formula was analyzed using simplex lattice design method. The results showed that increasing proportion of Carbopol 940 increased the tablet hardness and mucoadhesive strength and increasing the proportion of HPMC K15M reduced the drug release. Optimum formula was obtained at proportion of HPMC K15M 30,610 mg and Carbopol 940 mg 19,390 mgKeywords : Nifedipin, mucoadhesive, HPMC K15M, Carbopol 940.Nifedipin merupakan golongan calcium channel blocker digunakan untuk terapi hipertensi. Nifedipin memiliki waktu paruh yang pendek (2-4 jam) dan diabsorbsi baik di lambung, sehingga nifedipin menjadi kandidat yang baik untuk dibuat sediaan mucoadhesive. Penelitian ini bertujuan mengoptimasi dan mengetahui pengaruh proporsi Carbopol 940 dan HPMC K15M terhadap sifat fisik tablet dan pola pelepasan zat aktif. Pembuatan tablet dilakukan secara metode granulasi kering dengan menggunakan konsentrasi HPMC K15M (A) dan Carbopol 940 (B) yang berbeda untuk tiap formula yaitu 0% A : 100% B, 25% A : 75% B, 50% A: 50% B, 75% A : 25% B, dan 100% A : 0% B. Bobot tiap tablet 250 mg dengan kandungan nifedipin 20 mg untuk setiap tablet. Kekuatan melekat tablet ditentukan dengan menggunakan lambung kelinci dan uji pelepasan obat menggunakan media dapar NaCl ditambah 0,5% natrium lauril sulfat pH 1,2 selama 6 jam. Formula optimum dianalisa dengan menggunakan simplex lattice design. Hasil menunjukkan bahwa peningkatan proporsi Carbopol 940 meningkatkan kekerasan tablet mucoadhesive dan daya mucoadhesive sedangkan peningkatan proporsi HPMC K15M akan memperlambat pelepasan zat aktif. Formula optimum diperoleh pada proporsi HPMC K15M 30,610 mg dan Carbopol 940 19,390 mg

OPTIMIZING FORMULATION OF MINI TABLETS FLOATING RANITIDINE HCL USING FULLY PREGELATINIZED STARCH (MANIHOT ESCULENTA CRANTZ) WITH SIMPLEX LATTICE DESIGN

Objective: The main objective of this study was to optimize the noneffervescent floating mini tablets (NEFT) formula of ranitidine hydrochloride (ranitidine HCl) using the simplex lattice design (SLD) with parameters, granule flow rate, hardness, friability, floating lag time and ranitidine HCl dissolution test (%). Methods: The material was prepared using the SLD model was cassava starch fully pregelatinized (CSFP), hydroxypropyl methylcellulose K4M (HPMC K4M), and magnesium stearate. The formula obtained was tested for critical parameters, namely flow rate, hardness, friability, floating lag time and ranitidine HCl dissolution test (%). The dissolution test was carried out by using the USP type II method (paddle method). The beaker is immersed in the water bath of temperature 37 °C. It is filled with 900 ml of 0.1 N HCl, and the apparatus was set at 75 rpm. The samples were taken in the interval of 10 min and estimated content by a spectrophotometer at 312 nm. Results: The optimum formula based on superimposed graphs of various contour plots with SLD. From the experimental data for all test parameters, the experimental results are approaching with the results of the prediction. The condition for optimum functional components in NEFT was 80 mg for CSFP, HPMC K4M 30 mg, and 10 mg magnesium stearate to obtain a yield of 7.85 kg hardness, 0.34 % friability, 15.27 floating lag time and 91.31 % ranitidine HCl dissolved. Conclusion: It can be concluded that the optimum formula using the Design-Expert® program the SLD concept is obtained in the range of 70-80 mg CSFP, 30-40 mg HPMC K4M, 0-10 mg magnesium stearate

OPTIMIZATION OF PCL-PEG-PCL TRIBLOCK COPOLYMER MICELLES AS HYDROPHOBIC DRUG CARRIER WITH A 22 FULL FACTORIAL DESIGN

Objective: This study aims to optimize PCL-PEG-PCL (PCEC) triblock copolymer micelles as a hydrophobic drug carrier, simvastatin (SV). Methods: PCEC triblock copolymer was prepared by the ring-opening polymerization method (ROP) with different ɛCL/PEG ratio (2 and 5). SV was incorporated into the PCEC triblock copolymer micelles with a concentration of 2.5 and 10 % w/w by the solvent evaporation method (film formation). The influence of the ɛCL/PEG ratio and concentration of SV effect on the responses particle size (PS), polydispersity index (PI) and entrapment efficiency (EE) was assessed using 22 full factorial design method. The test results were analyzed using Design-Expert software to obtain the optimum formula. Result: The selection of the optimum formula is based on the desirability value, the formula with the largest desirability value is chosen as the optimum formula. The results showed the optimum formula chosen had a desirability value of 0.860 consisting of a ɛCL/PEG ratio of 5 and SV concentration of 10 % w/w, with the PS, PI dan EE value was 322.1±3.51 nm, 0.471±0.09 and 87.08±1.17 %, respectively. Conclusion: The 22 full factorial design has been proven to be used as an optimization method to determine the optimum formula of SV-loaded PCEC triblock copolymer micelles with a good result of the PS, PI and EE responses