Formulasi dan Evaluasi in Vitro Film Transdermal Natrium Diklofenak Menggunakan Polimer Kitosan dan Polivinil Alkohol Taut Silang Natrium Tipoli Fosfat

Abstract

Latar belakang: Natrium diklofenak termasuk obat anti inflamasi non steroid yang memiliki efek anti radang dan nyeri. Pemberian natrium diklofenak secara transdermal dapat mengontrol pelepasan natrium diklofenak dari basisnya, diharapkan dapat menghindarkan efek samping pada lambung dan first pass metabolismdi hati. Tujuan: Penelitian ini bertujuan untuk memformulasi film transdermalnatrium diklofenak denganteknik taut silangmenggunakan polimer kitosan, polivinil alkoholdan natrium tripoli fosfat. Metode:Film transdermal dibuat dengan mencampurkan larutan chitosan dan larutan polivinil alkohol dengan penambahan gliserin dan natrium diklofenak hingga terbentuk film lalu dikeringkan.Teteskan larutan natrium tripoli fosfat hingga terjadi reaksi taut silang, lalu dikeringkan.Film transdermal dibuat dalam enam formula menggunakan kitosan (2%), polivinil alkohol (8%) dengan perbandingan 30:70penambahanlarutannatriumtripolifosfatwaktutaut silang10 menit(F1) dan 20 menit (F2),50:50waktu taut silang10 menit(F3) dan 20 menit (F4),70:30 waktutaut silang10 menit(F5) dan 20 menit (F6). Evaluasi karakter film meliputi pengamatan organoleptis, uji bobot, ketebalan, kandungan kelembaban (%), daya lipat, interaksi antar bahan, kadar zat aktif. Pelepasan obat ditentukan menggunakan sel difusi Franz dalam buffer fosfat (pH7,4). Hasil: Pengamatan organoleptis menunjukkan seluruh filmberwarna kuning dengan kehalusan yang berbeda. Formula F1, F2, F3 dan F4 menghasilkan filmdengan tekstur halus, formula F5 dan F6 menghasilkan filmdengan tekstur kasar. Formula F1, F2, F5 dan F6 bersifat lentur dan memenuhi syarat uji daya lipat, sedangkan formula F3 dan F4 tidak lentur dan tidak memenuhi syarat lipat.Seluruh film transdermal memenuhi syarat uji keseragaman bobot, ketebalan dan kandungan kelembaban. Kandungan kelembaban terendah dimiliki oleh formula F1, yaitu 1,07±0,193%.Formula F1 juga memiki persen kumulatif optimal (94,30%) dan natriumdiklofenakterlepassebanyak 17,89 μg, flukspelepasan 894,42 μg/cm²/ jam waktupermeasi 10 jam, %. Ujipenetrasisecarain vitro film transdermal natriumdiklofenakmenunjukkanformulasidengan waktu taut silang 10 menitmemulikipersenkumulatifdanflukspelepasanlebihbaikdariwaktu taut silang 20 menit.Pelepasanfilmtransdermal natrium dikofenak mengikuti pelepasan orde nol mekanisme erosi. Pemeriksaan FTIR menunjukkan tidak adanya interaksi antara natrium diklofenak dan eksipien. Kesimpulan: Filmnatrium diklofenak dapat dibuat dengan metode taut silang menggunakan polimer kitosan, polivinil alkohol dan natrium tripoli fosfat. Pembuatanfilmtransdermal dengan waktu taut silang 10 menit menghasilkan profil pelepasan yang lebih baik dibandingkan waktu taut silang 20 menit.

Background: Diclofenac sodiumwas included in non-steroidal anti-inflammatory, used as anti inflammation.Transdermal administration of diclofenac sodium could controlled the release of diclofenac sodium from its base, its expectedto avoid side effects on the stomach and first pass metabolism inhepar. Objective:The aim of this study was to formulate a diclofenac sodium transdermal used chitosan and polivinil alcohol polimers or crosslinked with sodium tripolyphosphate. Method: Transdermal film was made by mixing chitosan solution and polyvinyl alcohol solution and then glycerin and diclofenac sodium was added until a film was formed then dried. Sodium tripoli phosphate solution was dripped until a cross-linked reaction occurs, then dried. Transdermal film was made in formula six using chitosan (2%), polyvinylohol (8%) with a ratio of 30:70 was added with sodium tripoli phosphate, crosslinkedtime 10 minutes (F1) and 20 minutes (F2), 50:50time 10 minute (F3) and 20 minute (F4), 70:30 time 10 minutes(F5) and 20 minute (F6). Evaluation of film characters included organoleptic observation, weight test, thickness, moisture uptake (%), folding endurance, interaction between materials, levels of active substances. The drug release corresponded to the Franz diffusion cell in a phosphate buffer (pH7.4). Results: Organoleptic observations showed all films are yellow with different uniformity. Formula F1, F2, F3 and F4 produced films with fine textures, the F5 and F6 formulas produced films with a coarse texture. Formula F1, F2, F5 and F6 were flexible and fulfilled the folding endurance test requirements, while the formula F3 and F4 were not flexible and did not met the folding endurance test requirement. Overall the transdermal film met the test requirements for uniformity, thickness and moisture uptake (%). The lowest mouisture uptake possessed by Formula F1, which is 1.07 ± 0.193%. Formula F1 also had an optimal cumulative percent (94.30%) and sodium diclofenac as much as 17.89 μg, release flux 894.42 μg / cm² / hour permeation time of 10 hours. In vitro penetration test of diclofenac sodium transdermal film showed the formulation with a 10 minute cross link time cumulative percent and release flux better than the 20 minute cross link time. The release of sodium transdermal film was enriched by the release of zero order erosion conditions. FTIR indicate showedthere nointeraction between diclofenac sodium and exipient. Conclusion: Diclofenacfilmnatrium could be made by crosslinking method using chitosan, polyvinyl alcohol and sodium tripoli phosphate. Filmtransdermal withtime 10 minute crosslinked produced a better release flux profile than the 20 minute crosslinked time.