Pengaruh Sifat Fisikokimia Beberapa Antihistamina terhadap Proses Traspernya Melewati Membran PHYSICOCHEMICAL INFLUENCE OF SOME arvtihistamines TO THEIR TRANSPORT TO PASS THROUGHT THE CELLOPHANE MEMBRANE

Antihistamina seperti CTM, difenhidramina HO, prometazina HCl dan astemizol mempunyai struktur kimia yang berbeda, sehingga senyawa-senyawa tersebut mempunyai sifat .fisikokimia yang berbeda pula. Perbedaan sifat fisikokimia akan berpengaruh terhadap interaksi dengan membran yang dilewatinya. Penelitian ini ingin mempelajari pengaruh sifat:fisilcokimia beberapa antihistamina terhadap transpor melewati membran selofan. Percobaan transpor dilakukan dengan menggunakan alai sel difusi model Goldberg dan Higuchi yang dimodifilcasi. Hasil penelitian menunjukkan bahwa transpor senyawa yang digunakan dalam melewati membran selofan mengikuti kinetika orde nol. Koefisien partisi sangat berpengaruh terhadap permeabilitas membran selofan dan harga logaritma koefisien partisi optimal antihistamina dalam melewati membran selofan adalah 2,0. Kata kunci: transpor antihistamina, CTM, difenhidramina HCI, prometazina HCI, astemizol, membran selofan, koefisien partisi optima

Difusi astemizol melewati membran isopropil miristat: As7emizole diffusion through isopropyl myrisstate membrane

Astemizol adalah antihistamina HI yang paten don mengalami metabolisme ekstensif di dalam hati. Salah satu alternatifuntuk menghindari metabolisme itu adalah astemizol digunakan secara transdermal. Penghalang utama obat melewati kulit adalah stratum korneum yang sering disimulasikan dengan membran Millipore yang diimpregnasi dengan isopropil miristat. Penelitian ini dilakukan untuk mengetahui difusi astemizol melewati membran yang merupakan simulasi kulit, dibuat dengan cara Millipore diimpregnasi dengan isopropil miristat. Media penerima yang digunakan adalah larutan dapar fosfat pH 6,0 dengan konsentrasi 0,01 M. Percobaan difusi dilakukan dengan menggunakan alat difusi model Goldberg dan Higuchi yang dimodijikasi pada suhu 30r, 3 7 r, dan 45\u27C. Hash, percobaan menunjukkan bahwa difusi astemizol melewati membran yang diimpregnasi dengan isopropil miristat mengikuti kinetika orde nol dengan energi penghalang adalah sehesar 6.251 kal/mol. lnteraksi yang lerjadi antara membran dengan astemizol berlangsung secara spontan. Berdasarkan harga entalpi ikatan yang lerjadi terutama karena ikatan hidrogen, sedangkan harga entropi memberikan indikasi bahwa sistem menjadi lebih acak. Kata kunci: Astemizol, difusi , membran impregnasi isopropil mirista

KINETlKA DAN MEKANISME TRANSPOR BEBERAPA ANTIHISTAMINA MELEWATl MEMBRAN SELOFAN

CTM, difenhidramina HCL prometazina HCL dan astemizol adalah antihistamina dengan struktur yang berbeda, sehingga senyawa-senyawa tersebut mempunyai sifat fisikokimia yang berbeda pula. Difusi antihistamina melewati membran dipengaruhi oleh sifat fisikokimia seperti kelarutan, koefisien partisi dan konsentrasi. Perbedaan sifat fisikokimia ini akan berpengaruh pada transpor antihistamina dalam melewati membran. Penelitian ini dilakukan dengan tujuan untuk mempelajari sifat fisikokimia dari keempat antihistamina tersebut diatas dan hubungan antara sifat fisikokimia tersebut dengan transpomya melewat membran selofan. Sifat fisikokimia yang diteliti meliputi suhu lebur, kelarutan dalam dapar fosfat 0,01 M pH 6,0 dan koefisien partisi dalam pelarut oktanol/dapar fosfat 0,01 MpH 6,0. Percobaan transpor dilakukan dengan menggunakan alat sel difusi model Goldberg dan Higuchi yang dimodifikasi. Membran yang digunakan sebagai membran selofan. Hasil penelitian menunjukkan bahwa harga koefisien partisi berturut-turut dari yang tertinggi ke yang terendah adalah astemizol, prometazina Hel, difenhidramina HCI, dan ClM. Kelarutan antihistamina dalam dapar fosfat 0,01 MpH 6,0 berturutturut dati yang terbesar ke yang terkecil adalah prometazina HC~ difenhidramina HC~ elM, dan yang terkecil adalah astemizol. Suhu lebur berturut-turut dati yang tertinggi ke yang terendah adalah prometazina HC~ astemizoI, difenhidramina HC~ dan ClM. Transpor senyawa yang digunakan dalam melewati membran mengikuti kinetika orde nol. Lipofilisitas senyawa yang tercermin dati harga koefisien partisi sangat berpengaruh terhadap transpor senyawa melewati membran selofan. Selain itu, bobot molekul juga berperan dalam melewati membran selofan. Interaksi antara membran dengan senyawa berlangsung spontan. Berdasarkan nilai entalpi interaksi yang terjadi antara membran dengan antihistamina terutama merupakan ikatan hidrogen. Nilai entalpi menunjukkan bahwa sistem menjadi Iebih acak

Effect of Lipid Ratio of Stearic Acid and Oleic Acid on Characteristics of Nanostructure Lipid Carrier (NLC) System of Diethylammonium Diclofenac

The aim of this study was to determine the effect of lipid ratio of stearic acid and oleic acid on the physical characteristics as well as the entrapment efficiency of diethylammonium diclofenac with Nanostructure Lipid Carrier (NLC) system. Diethylammonium diclofenac (DETA) is Non-Steroid Anti-Inflamatory Drugs (NSAIDs) that has been widely used in the treatment of osteoarthritis and rheumatoid arthritis. In the formulation of NLC-DETA, three different lipid ratios were used, which the ratio of  stearic acid:oleic acid were 60:40, 70:30, and 80:20, respectively. In this NLC system, DETA served as the active drug, stearic acid as solid lipid, oleic acid as liquid lipid, and Tween 80 as surfactant components. NLC were characterized for organoleptic characteristics, pH, viscosity, particle morphology, particle size and polydispersity index (PI), profiles of Fourier Transform Infra-Red (FTIR) and Differential Thermal Analysis (DTA), and drug entrapment efficiency. The particle shape and morphology were determined by Transmission Electron Microscopy (TEM). The results  showed that the different ratios of oleic acid lipids and stearic acid had no significant effects on the viscosity and entrapment efficiency of NLC-DETA. On the other hand, it affected the pH of all formulas, which were significantly different. Increasing the amount of liquid lipid in the formulations reduced the size of NLC-DETA particles.

PARTICULATE DELIVERY SYSTEM OF CHITOSAN - DITERPENE LACTONE FRACTION OF SAMBILOTO (ANDROGRAPHIS PANICULATA NEES): PREPARATION, CHARACTERIZATION AND IN VITRO DRUG RELEASE

Objective: This paper was aimed to study the effect of chitosan, sodium tripolyphosphate (TPP) as crosslinker, and diterpene lactone fraction of sambiloto (FDTL) from Andrographis paniculata Nees which contained 75.9% andrographolide on the characteristics of the FDTL-chitosan particulate system. Those characteristics were the physicochemical interaction, physical state, morphology, and drug entrapment efficiency. The in vitro drug release of the selected FDTL-chitosan particulate system was also evaluated.Methods: The particulate system of FDTL-chitosan was prepared by ionic gelation–spray drying method with the various amounts of TPP, chitosan, and FDTL. The physical characteristics were evaluated using Fourier transform infrared (FTIR), differential thermal analyzer (DTA), and X-ray diffraction, scanning electron microscope. In vitro drug release was performed in 0.1% sodium lauryl sulfate media at 37°C.Results: The results of FTIR and DTA analysis were in accordance with the results of morphology evaluation which indicated that chitosan-TPP ratio 10:8 could produce chitosan particles with a spherical and smooth surface. FDTL has been trapped in chitosan particulate systems, and the crystallinity of FDTL changed. Particulate systems with FDTL-chitosan-TPP ratio - 4:10:8 showed better characteristics compared to others with entrapment efficiency of 33.82%. The dissolution efficiency at 360 minutes (ED360) of particulate systems FDTL-chitosan was higher up to 1.5 times compared to FDTL.Conclusion: The difference in the ratio of chitosan and TPP affected the morphology of chitosan particles since the amount of drug loaded, and the amount of chitosan affected the drug entrapment. The ED360 of FDTL of FDTL-chitosan-TPP increased up to 1.5 times compared to the FDTL

Formulation and evaluation of erythropoietin-alginate microspheres at different amount of drug

This research formulate erythropoietin-alginate microspheres and to evaluate characteristics of erythropoietin-alginate microspheres at different amount of drug using aerosolization. Amount of erythropoietin are 10.000 IU (F1); 20.000 IU (F2); 60.000 IU (F3). The mixture of erythropoietin-alginate was sprayed into CaCl2 and was stirred at 1000 rpm for 30 minutes. Formulas resulted spherical shape of microspheres. The size of microspheres was 2.77 µm for F1; 3.89 µm for F2; and 4.42 µm for F3. The results of swelling index showed that swelling index of microspheres increased by increasing the concentration of erythropoietin. The results were in accordance with the size of the microspheres that increased with increasing concentration of drug. The yields of microspheres obtained were respectively 91.92%; 87.53%; 86.50% for F1, F2 and F3. It can be concluded that the particle size of microspheres, swelling index increased by increasing concentration of erythropoietin. In contrast, yield of microspheres decreased by increasing drug concentration. In conclusion, formula of microspheres were potential in terms of characteristics and may recommend for further in vivo study.

EFFECTIVITY AND PHYSICOCHEMICAL STABILITY OF NANOSTRUCTURED LIPID CARRIER COENZYME Q10 IN DIFFERENT RATIO of LIPID ALFA CETYL PALMITATE AND ALPHA TOCOPHERYL ACETATE AS CARRIER

Objective: The aim of this study was to investigate physical characteristics of nanostructured lipid carriers (NLCs) mixture of alpha tocopheryl acetate, cetyl palmitate, Tween 80 and propylene glycol using high shear homogenization technique on NLC preparation to predict the optimum ratio of alpha tocopheryl acetate-cetyl palmitate to produce good characteristics of NLC loaded coenzyme, higher % EE, good penetration, controlled release, and stable.Methods: Lipid characterizations were conducted by diffraction scanning calorimetry, X-ray diffraction, and Fourier transforms infrared spectrophotometry. Coenzyme Q10 concentration was measured by spectrophotometer at 275 nm. NLC characteristics based on their morphology was determined using transmission electron microscope, particle size, and its polydispersity index which were measured with Delsa Nanoâ„¢ particle size analyzer. Percentage of coenzyme Q10 entrapped in NLC was determined by dialysis bag method. Coenzyme Q10 release profile was measured using with Franz cell for 12 hrs. The penetration depth of NLC coenzyme Q10 in abdominal skin of Wistar rat was determined with fluorescence microscopy using rhodamine B as marker. NLC physical stability based on minimum of particle size variation, pH and viscosity during 90 days storage.Results: The result showed that formula with ratio of cetyl palmitate-alpha tocopheryl acetate 70:30 (% w/w) produce good characteristics of NLCloaded coenzyme, higher % EE, good penetration, controlled release, and stable in 90 days storage.Conclusion: The coenzyme Q10 NLC system with cetyl palmitate and alpha tocopherol acetate as lipid matrixare characterized by small particle size, low crystallinity, spherical morphology of particle and high coenzyme Q10 entrapment efficiency. Crystal modification led to the formation of a more amorphous thereby increasing the drug entrapmentKeywords: Coenzyme Q10, Nanostructured lipid carrier, Cetyl palmitate, Alpha tocopheryl acetate, High shear homogenization

Uji Efektivitas In Vitro (Penetrasi) Piroksikani dan Karakteristik Fisikokimia Sediam Piroksikam 0,5% dalam Basis Gel HPC dengan Penambahan Berbagai Macam Enhancher

Telah diteliti pengaruh beberapa enhancher terhadap penetrasi piroksikam dalam basis gel HPC. Digunakan beberapa enhancher yaitu propilenglikol, etanol, asam oleat dan tween 80, dengan konsentrasi 15%; 17,5%; 20% untuk propilengli kol, 5%; 7,5%; 10% untuk etanol, 0,5%; 1,0%; 1,5% untuk asam oleat dan 0,5%; 1,0%; 1,5% untuk tween 80. Sebagai basis gel digunakan HPC dengan konsentrasi 2% dan sebagai bahan aktif digunakan piroksikam dengan konsentrasi 0,5%. Pengujian terhadap sediaan meliputi pemeriksaan organoleptis (warna, bau, konsistensi), pH sediaan , daya sebar dan uji penetrasi dengan menentukan harga fluks dan permeabilitas.Uji penetrasi dilakukan menggunakan sel difusi dengan media larutan dapar fosfat pH 1,2 ± 0,05 pada suhu 37 ± 0,5°C serta membran Millipore yang diimpregnasi dengan isopropyl miristat. Data data yang diperoleh dari hasil pemeriksaan dan perhitungan dianalisa dengan statistik anova one way yang dilanjutkan dengan pengujian nilai HSD. Hasil identifikasi bahap penelitian, secara keseluruhan telah menunjukkan kesesuaian.dengan sertifikat analisis maupun spesifikgsi dalam pustaka. Penambahan propilenglikol 15%; 17,5%; 20% pada sediaan tidak berpengaruh terhadap harga pH dan daya sebar sediaan. Penambahan propilenglikol meningkatkan harga fluks piroksikam dan permeabilitas membran. Keadaan optimal dicapai pada konsentrasi propilenglikol 17,5%, yaitu fluks meningkat 38% dan permeabilitas meningkat 36%. Sedangkan pada konsentrasi 20% terjadi penurunan sehingga tidak berbeda dengan kontrol

PREPARATION AND EVALUATION OF CIPROFLOXACIN IMPLANTS USING BOVINE HYDROXYAPATITE-CHITOSAN COMPOSITE AND GLUTARALDEHYDE FOR OSTEOMYELITIS

Objective: The objective of this study was to develop and evaluate a controlled release implant of ciprofloxacin using Bovine Hydroxyapatite-Chitosan composite and glutaraldehyde as cross-link agent.Methods: Ciprofloxacin implants were prepared using Bovine Hydroxyapatite-Chitosan composite composition 70:30. This composite was further developed using three different concentrations of glutaraldehyde (0.5%, 0.75%, and 1,0%). Implants were formed into pellets with 4.0 mm diameters and weighed 100.0 mg using compression method. Further, the prepared ciprofloxacin implants were characterized for porosity, density, water absorption capacity, swelling ratio, degradation test, compressive strength, compatibility studies (FT-IR), morphology (SEM), X-ray diffraction study, assay, and in vitro drug release.Results: The addition of glutaraldehyde as cross-link agent in ciprofloxacin implants showed controlled release profile of ciprofloxacin over a time period 30 d. This is caused by glutaraldehyde formed compact structure, so the porosity, water absorption capacity, and swelling ratio of the implants decreased. Scanning Electron Microscope photomicrograph revealed low porosity of the implants after cross-linking with glutaraldehyde. The FTIR study confirmed the formation of covalent imine bonds between Chitosan and glutaraldehyde. However, the addition of glutaraldehyde as a cross-link agent caused a decrease in the mechanical strength of the implants. Increased concentration of glutaraldehyde reduced the cristalinity of BHA and Chitosan, which were confirmed by XRD studies. In consequence, the mechanical strength of the implants decreases.Conclusion: The results obtained from this study indicated that glutaraldehyde has the potential effect to retard ciprofloxacin release from Bovine Hydroxyapatite-Chitosan-ciprofloxacin implants for 30 d in the treatment of osteomyelitis.Â

The release of sodium diclofenac from matrix type of transdermal patch

Pelepasan natrium diklofenak dari Sediaan Transdermal Patch Tipe Matriks dengan kombinasi polimer etil selulosa (EC) N-20 dan polivinilpirolidon (PVP) K-30 telah diteliti. Pada penelitian ini sediaan transdermal patch tipe matriks yang mengandung natrium diklofenak dibuat dengan kombinasi polimer etil selulosa (EC) N-20 dan polivinilpirolidon (PVP) K-30 pada perbandingan yang berbeda ( 9:1 (Formula I); 8:2 (Formula II); dan 7:3 (Formula III)). Persentase (%) moisture content dihitung dari perbedaan berat relatif pada penimbangan akhir. Uji homogenitas permukaan patch dilakukan dengan menggunakan metode Scanning Electron Microscopy (SEM). Uji disolusi dengan media larutan dapar fosfat salin pH 7,4 ± 0.05 sebanyak 500,0 mL yang terlebih dahulu dipanaskan sampai mencapai temperatur percobaan 37 ± 0.5°C diaduk pada kecepatan 50 rpm. Hasil dianalisis menggunakan SPSS dengan metode ANOVA one way dengan tingkat kepercayaan 95% (α = 0,05). Berdasarkan penelitian ini, penggunaan polimer kombinasi antara etil selulosa (EC) N20 dan polivinilpirolidon (PVP) K-30 dapat meningkatkan fluks pelepasan natrium diklofenak dari sediaan patch natrium diklofenak. Perbandingan 7:3 dari etil selulosa (EC) N-20 dan polivinilpirolidon (PVP) K-30 adalah kombinasi yang terbaik untuk sediaan patch natrium diklofenak karena konsistensi bentuk fisik serta nilai fluks pelepasan dan penetrasi yang dihasilkan lebih besar dari perbandingan lainnya