Formulasi Transdermal Patch Dispersi Padat Meloksikam sebagai Analgesik dan Antiinflamasi

Abstract

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID), an enolic acid derivative that inhibits the cyclooxygenase-2 (COX-2) enzyme. and is usually used by the oral route in the treatment of a wide variety of rheumatic diseases, including rheumatoid arthritis (RA), osteoarthritis, low back pain and various other joint diseases. However, when given, meloxicam is given orally, causing gastrointestinal side effects such as bleeding, gastric ulcers, nausea and vomiting, which can occur at any time when given orally. So that to avoid these side effects, it can be formulated into transdermal patch solid dispersion. Transdermal patches of meloxicam solid dispersion was prepared with a mixture of polymer hydroxypropyl methylcellulose, ethyl cellulose and polyvinylpyrrolidone and various concentration of propylene glycol, that were F1 10%; F2 20% and F3 30%. The prepared of transdermal patches of meloxicam solid dispersion was evaluated for various physicochemical parameters, organoleptic, thickness, weight uniformity, folding resistance, moisture content, and swelling properties. Interaction between active smeloxicam and polymers using FTIR, analysis crystal structure by X-ray diffraction, in-vitro drug penetration (franz diffusion cell). The best formulas was evaluated in vivo to comparing their analgesic and antiinflammatory activities with those of marketed gel Transdermal patches of meloxicam solid dispersion prepared from three formulas were yellow, odorless, dry and flat surface, thickness between 0.0193 to 0.0212 cm, weight uniformity of weight 98.88 to 123.26 mg, folding resistance 370 to 375 times, moisture content 2.094 to 2.410% and swelling 7.49 to 19.10%. Transdermal patches of meloxicam solid dispersion penetration of F3 at -480 minutes of the highest % penetration, that were, 86,453%,, AUC value of 1867.303 (% .minutes), so it can be concluded that the use of various concentrations of propylene glycol as an enhancer affects drug release. The results of FTIR analysis that there is no interaction the active substance of meloxicam and the polymer. The analgesic effect of F3 was highest at 260 minutes, that were 61,98 (seconds), while the sodium diclofenac gel at 240 minutes was 43,51 (seconds) and percentage of anttiinflamation inhibition at 480 minutes was 90.10%, while sodium diclofenac gel at 480 minutes was 64,61%. Transdermal patches of meloxicam (F3) solid dispersion show better analgesic and anti-inflammatory effects than other formulas and diclofenac sodium gel.

Meloksikam merupakan obat golongan non steroidal antiinflamantory drug (NSAID) turunan asam enolat yang menghambat enzim siklooksigenase-2 (COX-2) dan biasanya digunakan dengan rute peroral dalam pengobatan berbagai macam penyakit rematik, termasuk rheumatoid arthritis (RA), osteoarthritis, nyeri pinggang dan berbagai penyakit sendi lainnya. Pada pemberian secara peroral menyebabkan efek samping pada saluran pencernaan, untuk menghindari efek samping tersebut dapat diformulasikan menjadi transdermal patch dispersi padat. Transdermal patch dispersi padat meloksikam dibuat dengan campuran polimer hidroksipropil metilselulosa, etil selulosa dan polivinilpirolidon dengan berbagai variasi konsentrasi propilen glikol yaitu F1 10%; F2 20% dan F3 30%. Pembuatan transdermal patch dispersi padat meloksikam dievaluasi untuk berbagai parameter yaitu fiskokimia, organoleptis, ketebalan, keseragaman bobot, ketahanan lipat, moisture content, dan swelling. Interaksi antara zat aktif dan polimer menggunakan FTIR, analisis struktur kristal menggunakan difraksi sinar-x (XRD), penetrasi obat in-vitro (sel difusi franz). Formula terbaik dievaluasi in vivo untuk membandingkan aktivitas analgesik dan antiinflamasinya dengan gel yang dipasaran. Transdermal patch dispersi padat meloksikam yang dibuat dari tiga formula menunjukkan hasil patch berwarna kuning, tidak berbau, permukaan kering dan rata, ketebalan antara 0,0193 sampai 0,0212 cm, keseragaman bobot antara 98.88 sampai 123,26 mg, ketahanan lipat antara 370 sampai 375, moisture content antara 2,094 sampai 2,410% dan swelling antara 7,49 sampai 19,10%. Sediaan transdermal patch dispersi padat meloksikam F3 pada menit ke-480 menunjukkan % terpenetrasi yang paling tinggi yaitu 86,453%, nilai AUC sebesar 1854,353 (%.menit), sehingga dapat disimpulkan bahwa penggunaan variasi konsentrasi propilen glikol sebagai enhancer mempengaruhi pelepasan obat. Hasil analisis XRD dan FTIR menunjukkan tidak adanya interaksi antara zat aktif meloksikam dengan polimer. Efek analgesik F3 tertinggi pada menit ke-360 yaitu 61,98 (detik), sedangkan gel natrium diklofenak pada menit ke-240 yaitu 43,51 (detik) dan persen inhibisi radang pada menit ke-480 90,10%, sedangkan gel natrium diklofenak pada menit ke-480 yaitu 64,61%. Transdermal patch dispersi padat meloksikam F3 menunjukkan efek analgesik dan antiinflamasi yang lebih baik dibandingkan formula lainnya dan gel natrium diklofenak.