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

Optimasi formula tablet gastroretentive ranitidin HCIdengan sistem floating = Optimization formula gastroretentive tablet of ranitidine HCIwith floating system

Ranltldin HCI merupakan antagonis reseptor H-2 untuk terapi sekresi tukak lambung dengan bioavailabilitas kecil, sehlngga perlu dlkembangkan dalam bentuk sedlaan sustained release yang ditahan di lambung. Formulasi floating tablet ranitidln HCI dlbuat menggunakan slstem effervescent. Simplex lattice design digunakan untuk optlmasi formula sediaan floating tablet ranltldln HCI dengan varlasl kadar Methocel K15M 100-185 mg, natrium blkarbonat 15-100 mg, dan asam sltrat 0-85 mg. Penentuan area formula optimum dltentukan berdasarkan superimposed contour plot berbagai parameter: sifat allr granul, sifat. flslk tablet dan pelepasan obat dengan menggunakan program Design [email protected] superimposed contour plot dlperoleh area formula optimum pada rentang Methocel K15M 100-145 mg, natrium blkarbonat 20-80 mg asam sltrat dan 25-80 mg. Ranltldine HCIis an H-2 receptor antagonists for the treatment of peptic gastric secretion with a small bloavailabllity, so that should be developed in a sustained release dosage form are retained in the stomach. Ranitidine HCI floating tablet was formulation by effervescent system. Simplex lattice design was applied to optimize the formula of ranitidine HCI floating tablet by varying levels of Methocel K15M 100-185 mg, sodium bicarbonate 15-100 mg, and citric acidO-85 mg. The Optimum formula determined by superimposed contour plot from various parameters: flowability of granules, physical properties of tablet and drug release using Deslgn-Expert@program. Based on superimposed contour plot obtained optimum formula for the area in the range of Methocel K15M100-145 mg, sodium bicarbonate 20-80 mg and citric acid 25- 80 mg

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

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

Mouthwash Formulation Of Basil Oil (Ocimum Basilicum L.) And In Vitro Antibacterial And Antibiofilm Activities Against Streptococcus Mutans

Basil leaves (Ocimum basilicum L.) contain essential oil that have been reported to have antibacterial activity. Based on this antibacterial activity, basil oil can be developed as mouthwash to prevent a dental plaque. This study aims to investigate the influence of tween 80 (as emulsifying agent) and glycerin (as stabilizer) on physical characteristics of the mouthwash, the ratio between tween 80 and glycerin for best stability, and in vitro antibacterial and antibiofilm activity of the mouthwash against Streptococcus mutans. Basil oil was extracted by water and steam distillation, then was formulated into mouthwash with a variation amount of tween 80 and glyserin. Antibacterial and antibiofilm activities weretested with micro dilution method. Result of study showed that tween 80 gives significant increase on viscosity and glycerin on specific mass when they were added at more than 2.5 mL in 50 mL mouthwash. From five formulas, formula with ratio of tween 80 and glycerin = 3.75 mL : 1.25 mL was found to be the best. Basil mouthwash showedin vitro antibacterial and antibiofilm activities against Streptococcus mutans. This product had MIC of 0.1 % v/v with 87,50 ± 3,33 % of bacterial inhibition. The MIC of biofilm formation and biofilm degradation was 0.1 % v/v and 0.2 % v/v, with % inhibition and degradation of 77,52 ± 0,82 % and 57,64 ± 6,09 %, respectively

FORMULATION AND IMMUNOSTIMULANT STABILITY POLYSACCHARIDE SYRUP OF FRACTION NONI (MORINDA CITRIFOLIA L.) FRUITS

Objective: The study aimed to formulate standardized polysaccharide fraction of Noni (SPFN) fruit into syrup preparations to fulfill the acceptability requirement of National Agency of Drugs and Food Control [Badan Pengawas Obat dan Makanan Republik of Indonesia (BPOM RI)] so that it can be used in the community as an immunostimulant. Methods: The optimization of the formula A and B were done using Simplex Lattice Design (SLD) method and its stability tested under extreme temperature change effect using thaw cycling method by evaluating the physical properties, microbial contamination and immunostimulant activity. MTT method was used to determine the immunostimulant activity of syrup against lymphocyte proliferation in vitro. Results: Based on the results of stability tests of formula A using pH (4.45), viscosity (81.03 mPas), taste (good taste), pouring power (2.31 s), amount of bacteria (68 colonies/ml), total yeast and mold (269 colonies/ml) parameters and fulfilled the acceptability requirement of BPOM RI. Formula A could maintain better stability than formula B. Formula A syrup used for immunostimulant activity testing that could increase lymphocyte proliferation at a concentration of 13.33 to 106.64 μg/μl and it’s stable under the influence of extreme temperature changes. Conclusion: Formula A could be used to produce SPFN syrup, which has stable physical properties and immunostimulant activity beside no microbial contamination that fulfill requirements of BPOM RI

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

Tunnelling Methods and Hawking's radiation: achievements and prospects

The aim of this work is to review the tunnelling method as an alternative description of the quantum radiation from black holes and cosmological horizons. The method is first formulated and discussed for the case of stationary black holes, then a foundation is provided in terms of analytic continuation throughout complex space-time. The two principal implementations of the tunnelling approach, which are the null geodesic method and the Hamilton-Jacobi method, are shown to be equivalent in the stationary case. The Hamilton-Jacobi method is then extended to cover spherically symmetric dynamical black holes, cosmological horizons and naked singularities. Prospects and achievements are discussed in the conclusions.Comment: Topical Review commissioned and accepted for publication by "Classical and Quantum Gravity". 101 pages; 6 figure

Layered hydroxide anion exchanger and their applications related to pesticides: a brief review

Layered double hydroxides and layered hydroxide salts have generated enormous excitement in the inorganic field due to their potential to act as versatile host materials in fabricating novel host–guest layered materials. The ability of the layered hydroxide anion exchanger to be incorporated with a wide range of guest ions enable them to be exploited in various applications related to pesticides. This review sums up the different methods of preparing layered hydroxide anion exchanger, summarises the types of anion intercalated into these layered hydroxide anion exchanger based on their respective systems, and elucidates their potential applications in pesticide-related fields

Circadian pacemaker coupling by multi-peptidergic neurons in the cockroach Leucophaea maderae

Lesion and transplantation studies in the cockroach, Leucophaea maderae, have located its bilaterally symmetric circadian pacemakers necessary for driving circadian locomotor activity rhythms to the accessory medulla of the optic lobes. The accessory medulla comprises a network of peptidergic neurons, including pigment-dispersing factor (PDF)-expressing presumptive circadian pacemaker cells. At least three of the PDF-expressing neurons directly connect the two accessory medullae, apparently as a circadian coupling pathway. Here, the PDF-expressing circadian coupling pathways were examined for peptide colocalization by tracer experiments and double-label immunohistochemistry with antisera against PDF, FMRFamide, and Asn13-orcokinin. A fourth group of contralaterally projecting medulla neurons was identified, additional to the three known groups. Group one of the contralaterally projecting medulla neurons contained up to four PDF-expressing cells. Of these, three medium-sized PDF-immunoreactive neurons coexpressed FMRFamide and Asn13-orcokinin immunoreactivity. However, the contralaterally projecting largest PDF neuron showed no further peptide colocalization, as was also the case for the other large PDF-expressing medulla cells, allowing the easy identification of this cell group. Although two-thirds of all PDF-expressing medulla neurons coexpressed FMRFamide and orcokinin immunoreactivity in their somata, colocalization of PDF and FMRFamide immunoreactivity was observed in only a few termination sites. Colocalization of PDF and orcokinin immunoreactivity was never observed in any of the terminals or optic commissures. We suggest that circadian pacemaker cells employ axonal peptide sorting to phase-control physiological processes at specific times of the day