FORMULASI SEDIAAN BUKOADHESIF FILM HIDROGEL GAMAVUTON-0 DENGAN MATRIKS KITOSAN DAN PVA SERTA EFEKNYA PADA JUMLAH SEL POLIMORFONUKLEAR DALAM PROSES PENYEMBUHAN LUKA MUKOSA BUKAL TIKUS WISTAR
NAJMA ANNURIA FITHRI, Dr.rer.nat. Ronny Martien, M.Si.,
2013 | Tesis | S2 Ilmu FarmasiLuka pada rongga mulut merupakan salah satu jenis luka yang umum terjadi dan menurut data tahun 2012 diderita oleh 15 – 20% penduduk dunia. Gamavuton-0 (GVT-0) merupakan salah satu senyawa analog kurkumin yang memiliki aktivitas antioksidan, antimikroba dan antiinflamasi. Aktivitasnya sebagai antiinflamasi belum diteliti lebih lanjut dalam proses penyembuhan luka. Penelitian ini bertujuan membuat formulasi sediaan film bukoadhesif GVT-0 dengan menggunakan campuran kitosan dan PVA serta mengkaji efeknya terhadap jumlah sel polimorfonuklear (PMN) mukosa bukal tikus Wistar dalam proses penyembuhan luka. Rancangan formula berdasarkan simplex lattice design dengan menggunakan software Design Expert®7.1.3. yang menghasilkan 8 run. Evaluasi karakteristik fisikokimia meliputi bobot, ketebalan, pH permukaan, indeks pengembangan, ketahanan lipatan, kandungan obat dan pelepasan obat secara in vitro. Formula optimum diuji secara ex vivo waktu mukoadhesif dan permeasi GVT-0 melewati membran mukosa bukal kelinci sebelum diuji efek in vivo. Pengujian in vivo dilakukan terhadap 48 ekor tikus putih jantan galur Wistar berumur 2 – 3 bulan dengan bobot 200 – 300 g, yang dibagi acak menjadi kelompok kontrol dan perlakuan. Tikus pada semua kelompok dikorbankan pada 1, 3, 5 dan 7 hari pasca perlukaan, dan jaringan mukosa area luka dibuat preparat histologis menggunakan pengecatan HE. Formula optimum diperoleh pada kadar kitosan sebesar 1,512% dan PVA 1,982%. Hasil formula optimum menunjukkan film dengan tampak visual yang baik dan fleksibel dengan bobot serta ketebalan yang seragam. Kadar GVT-0 di dalam sediaan berkisar antara 93 – 96% dengan pH permukaan 5 – 6 serta indeks pengembangan yang tinggi. Pelepasan GVT-0 dari sediaan mencapai 48,823 ± 0,348% dan waktu mukoadhesif 153 ± 2,870 menit dengan jumlah GVT-0 yang terpermeasi 2,020 ± 0,067%. Hasil pengujian in vivo menyimpulkan bahwa sediaan film bukoadhesif GVT-0 bermakna (p<0,050) menurunkan jumlah sel PMN dalam proses penyembuhan luka mukosa bukal.
Oral wound is one of the most prevalent inflammatory diseases in the society with around 15 – 20% of the world population affected. Gamavuton-0 (GVT-0) is an analogue compound of curcumin which possess a variety of pharmacological effects such as antioxidant, anti-microbial and antiinflammatory. Effect of GVT-0 on wound healing process has yet been observed. The aim of this study was to develop and create the optimum formula of GVT-0 buccoadhesive film using chitosan and PVA as well as to investigate its effect towards the number of polymorphonuclear (PMN) cells on Wistar rats. Film formulas were determined by using simplex lattice design method with software Design Expert 7.1.3. which resulted into 8 runs. The prepared films were characterized by using its film weight, thickness, surface pH, swelling index, folding endurance, drug content, and in vitro drug release profile. These characterizations were used to obtain the optimum combination formula of chitosan and PVA which then were analyzed to study buccal mucosa permeation transport and ex vivo residence time. In vivo study was conducted involving 48 male 2 – 3 months old and 200 – 300 grams in weight Wistar rats which then were divided randomly into control groups and treated group. The rats in all groups were sacrificed on day 1, 3, 5 and 7 after injury, then the wounded tissue were processed into histology specimen with HE staining. The optimum combination result of 1.518% chitosan and 1.982 % PVA showed that all films produced were good in appearance and flexibility. The weight and thickness were found to be uniform with the drug content ranging from 93 – 96 %. Swelling index showed favorable result with its pH ranging from 5 – 6. In vitro drug release of the optimum formulation showed that about 48.823 ± 0.348% of GVT-0 was released with a residence time of 153 ± 2.870 minutes. Buccal permeation test through rabbit buccal mucosa was found to be 2.020% ± 0.067 %. This study concluded that, the application of GVT-0 buccoadhesive films significantly (p<0.050) showed the ability to decrease the number of PMN cells significantly during wound healing process on buccal mucosa.
Kata Kunci : GVT-0, kitosan, PVA, film bukoadhesif, sel PMN
