0,OS). Dispersi padat furosemida - PVP 1 : 7 mempakan formula terbaik karena menghasilkan dengan ketersediaan hayati furosemida yang paling tinggi dan bioekivalen dengan formula Lasix@. Solid dispersion system of water-insoluble furosemide in polyvinylpirolidon (PVP) was prepared by a solvent method in various ratios of 1 : 5 and 1 : 7 of the drug and PVP, respectively in order to improve furosemide solubility, dissolution and bioavailability. The improvement of furosemide solubility was studied by a solubility method, using a shaking waterbath. The solubility test showed that PVP in various concentrations and temperatures provided statistically significant increases of furosemida solubility (P < 0’05). The interactions of furosemida - PVP complexes was confirmed by the results of infrared spectroscopy that showed the movement of functional groups. The dissolution study of furosemide solid dispersion system was done by a dissolution tester using the rate of rotation 50 rpm. Furosemide concentration was determined spectrophotometrically using a W spectrofometer. This test showed a significant increase in the extent of fbrosemida solubility (P 0,05), but with a prolonged of liberation time. The bioavailability of furosemide - PVP solid dispersion was compared with pure furosemide (control) and Lasix@ (reference). The study was done in a cross over design with a single-dose peroral that administered to the white male rabbits (n = 6). Furosemide blood levels were determined spectrofluorometrically by an extraction method. The area under the blood concentration-time curve AUCo - -, peak blood concentration GXan d time to reach peak blood concentration T, were used to compare their bioavailabilities. The solid dispersion systems produced a higher extent of bioavailability than pure furosemide (P < 0,05). On the contrary, no statistically significant difference the extent of bioavailability between solid dispersion and Lasix@ (P > 0,05). Finally, furosemide - PVP solid lspersion (1 : 7) was the best formulation with the highest extent of bioavailability and bioequivalence with the Lasix@ formula’s."> 0,OS). Dispersi padat furosemida - PVP 1 : 7 mempakan formula terbaik karena menghasilkan dengan ketersediaan hayati furosemida yang paling tinggi dan bioekivalen dengan formula Lasix@. Solid dispersion system of water-insoluble furosemide in polyvinylpirolidon (PVP) was prepared by a solvent method in various ratios of 1 : 5 and 1 : 7 of the drug and PVP, respectively in order to improve furosemide solubility, dissolution and bioavailability. The improvement of furosemide solubility was studied by a solubility method, using a shaking waterbath. The solubility test showed that PVP in various concentrations and temperatures provided statistically significant increases of furosemida solubility (P < 0’05). The interactions of furosemida - PVP complexes was confirmed by the results of infrared spectroscopy that showed the movement of functional groups. The dissolution study of furosemide solid dispersion system was done by a dissolution tester using the rate of rotation 50 rpm. Furosemide concentration was determined spectrophotometrically using a W spectrofometer. This test showed a significant increase in the extent of fbrosemida solubility (P 0,05), but with a prolonged of liberation time. The bioavailability of furosemide - PVP solid dispersion was compared with pure furosemide (control) and Lasix@ (reference). The study was done in a cross over design with a single-dose peroral that administered to the white male rabbits (n = 6). Furosemide blood levels were determined spectrofluorometrically by an extraction method. The area under the blood concentration-time curve AUCo - -, peak blood concentration GXan d time to reach peak blood concentration T, were used to compare their bioavailabilities. The solid dispersion systems produced a higher extent of bioavailability than pure furosemide (P < 0,05). On the contrary, no statistically significant difference the extent of bioavailability between solid dispersion and Lasix@ (P > 0,05). Finally, furosemide - PVP solid lspersion (1 : 7) was the best formulation with the highest extent of bioavailability and bioequivalence with the Lasix@ formula’s.">
Laporkan Masalah

Peningkatan kelarutan disolusi dan ketersediaan hayati furosemida melalui pembentukan dispersi padat

SYUKRI, Yandi, Dr. Lukman Hakim, MSc.,Apt

2001 | Tesis | S2 Farmasi

Sistem dispersi padat furosemida yang sukar larut dalam air dengan polivinilpirolidon disiapkan dengan metode pelarut dengan perbandingan 1 : 5 dan 1 : 7 dalam upaya meningkatkan kelarutan, disolusi dan ketersediaan hayati furosemida. Peningkatan kelarutan furosemida dilakukan dengan metode kelarutan menggunakan shaking wuterhulh. Uji kelarutan memperlihatkan bahwa PVP dengan berbagai kadar dan pada suhu yang berbeda meningakatkan kelarutan furosemida secara bermakna (P < 0,OS). Interaksi kompleks furosemida - PVP ditentukan dengan spektrum infra merah, yang menunj ukkan terjadinya pergeseran gugus fungsi akibat terjadinya kompleksasi. Uji disolusi sistem dispersi padat furosemida dilakukan menggunakan alat disolusi dengan kecepatan putar 50 rpm. Kadar furosemida terlarut ditentukan secara spektrofotometri UV. Uji ini memperlihatkan peningkatan jumlah furosemida yang terlarut secara bermakna (p < 0,05), tetapi tejadi penundaan waktu pelepasan awal. Ketersediaan hayati dispersi padat fkrosemida - PVP dibandingkan terhadap furosemida murni (kontrol) dan Lasix@ (pembanding). Percobaan dilakukan dalam suatu rancangan cross over dengan dosis tunggal peroral yang diberikan pada kelinci jantan putih (n = 6). Kadar furosemida dalam darah ditentukan secara spektrofluorometri dengan metode ekstraksi. Parameter yang digunakan untuk rnembandingkan masing-masing formula adalah luas daerah dibawah kurva AUC" - -, kadar puncak obat dalam darah C,, dan waktu untuk mencapai kadar puncak obat dalam darah T d s . Ketersediaan hayati dispersi padat ternyata lebih tinggi dibandingkan furosemida murni (P 0,05) . Sebaliknya, tidak memberikan perbedaan yang bermakna dibanhngkan Lasix@ (P > 0,OS). Dispersi padat furosemida - PVP 1 : 7 mempakan formula terbaik karena menghasilkan dengan ketersediaan hayati furosemida yang paling tinggi dan bioekivalen dengan formula Lasix@.

Solid dispersion system of water-insoluble furosemide in polyvinylpirolidon (PVP) was prepared by a solvent method in various ratios of 1 : 5 and 1 : 7 of the drug and PVP, respectively in order to improve furosemide solubility, dissolution and bioavailability. The improvement of furosemide solubility was studied by a solubility method, using a shaking waterbath. The solubility test showed that PVP in various concentrations and temperatures provided statistically significant increases of furosemida solubility (P < 0’05). The interactions of furosemida - PVP complexes was confirmed by the results of infrared spectroscopy that showed the movement of functional groups. The dissolution study of furosemide solid dispersion system was done by a dissolution tester using the rate of rotation 50 rpm. Furosemide concentration was determined spectrophotometrically using a W spectrofometer. This test showed a significant increase in the extent of fbrosemida solubility (P 0,05), but with a prolonged of liberation time. The bioavailability of furosemide - PVP solid dispersion was compared with pure furosemide (control) and Lasix@ (reference). The study was done in a cross over design with a single-dose peroral that administered to the white male rabbits (n = 6). Furosemide blood levels were determined spectrofluorometrically by an extraction method. The area under the blood concentration-time curve AUCo - -, peak blood concentration GXan d time to reach peak blood concentration T, were used to compare their bioavailabilities. The solid dispersion systems produced a higher extent of bioavailability than pure furosemide (P < 0,05). On the contrary, no statistically significant difference the extent of bioavailability between solid dispersion and Lasix@ (P > 0,05). Finally, furosemide - PVP solid lspersion (1 : 7) was the best formulation with the highest extent of bioavailability and bioequivalence with the Lasix@ formula’s.

Kata Kunci : Obat, Disolusi, Dispersi Padat, Solid dispersion, solubility, dissolution, bioavailability, furosemide.


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