Formulasi Sediaan Okular Gel Mukoadesif dan Termosensitif Vitamin A

SITI FATMAWATI FATIMAH, Prof. Dr. apt. Akhmad Kharis Nugroho, M.Si; Prof. Dr. rer.nat. apt. RR. Endang Lukitaningsih, M.Si; Dr.rer.nat. Ronny Martien, M.Si.

2025 | Disertasi | S3 Ilmu Farmasi

Mata adalah organ yang rentan terhadap stres oksidatif yang memicu katarak, retinopati diabetik, degenerasi epitel retina yang memicu degenerasi makula. Vitamin A terbukti meningkatkan respon antiinflamasi, meningkatkan musin air mata sel goblet dan sebagai antioksidan. Waktu tinggal prekornea yang singkat dan absorpsi tidak adekuat menyebabkan hanya 1-3% obat yang dapat menembus kornea. Tujuan penelitian adalah mengembangkan formula sediaan okular mukoadesif gel termosensitif nanoemulsi kationik vitamin A (GT-NEKA).

Capryol® 90, capric trigliserida sebagai fase minyak, Kolliphor® El, Transcutol® HP sebagai campuran surfaktan. Nanoemulsi kationik (NEKA) dibuat dengan metode water titration dengan agen kationik cetalkonium klorida. Poloxamer 407 dan poloxamer 188 merupakan basis gel termosensitif dan jumlahnya berdasar parameter suhu gelasi (TGel) dan diluted gelation temperature (TDill). GT-NEKA diuji morfologi, reologi, kadar, pelepasan, profil permeasi, keamanan, potensi antiinflamasi, aktivitas antiradikal bebas dan stabilitasnya. Penetapan kadar vitamin A GT-NEKA dengan instrumen HPLC, dan pada medium pelepasan serta medium permeasi dengan Spektrofotometer UV-vis divalidasi mengacu pada USP 46, NF 26 (2023).

Formula sediaan okular muokoadesif GT-NEKA mampu bertranfomasi sol-gel pada suhu mata, sifat alir pseudoplastis, profil pelepasan korsmeyer-peppas, dan jumlah kumulatif vitamin A yang terpermesi selama 4 jam (220,759?31,869) ?g. GT-NEKA telah terbukti aman tidak mengiritasi mata serta memiliki aktivitas antiradikal bebas IC50 (9,367?0,021) mg/mL dan potensi antiinflamasi IC50 (1,564?0,004) mg/mL. Metode analisis penetapan kadar vitamin A dengan instrumen HPLC dan Spektrofotometer UV-vis berhasil divalidasi.

Sediaan okular mukoadesif GT-NEKA berhasil diformulasikan, bersifat aman, tidak mengiritasi, mampu melepaskan dan menghantarkan vitamin A pada kornea mata, berpotensi menangkap radikal bebas dan sebagai antiinflamsi serta stabil dalam penyimpanan.

Eye is vulnerable to oxidative stress  from UV radiation and blue light exposure. Prolonged oxidative stress can lead to conditions, such as cataracts, diabetic retinopathy, and retinal epithelial degeneration, potentially resulting in macular degeneration. Vitamin A has been proven to enhance anti-inflammatory responses, increases mucin secretion from goblet cells in the tear film, and functions as an antioxidant. The short precorneal residence time and inadequate absorption result in only 1-3% of the drug penetrating the cornea. This study aimed to develop a mucoadhesive ocular formulation of cationic nanoemulsion vitamin A loaded to thermosensitive gel (GT-NEKA). 

Capryol® 90, capric trigliserida were selected as the oil phases, Kolliphor® El and Transcutol® HP served as surfactants. Cationic nanoemulsin (NEKA) was prepared using a water titration method with cetalkonium chloride as cationic agent. The characterization of NEKA included Z-average, PDI, zeta potential, morphology, pH, osmolality, percent transmittance, refractive index, and assay. Poloxamer 407 and poloxamer 188 were chosen as the thermosensitive gel bases for dispersing NEKA and their quantity were determined according to Gelation temperature (TGel) and diluted gelation temperature (TDill) parameters. GT-NEKA was evaluated for morphology, rheology, assay, vitamin A release profile, permeation study, safety, anti-inflammatory potential, free radical scavenging activity, and stability. The vitamin A determination of GT-NEKA using the HPLC instrument, and in the release medium and permeation medium using a UV-Vis Spectrophotometer, is validated according to USP 46, NF 26 (2023).

The mucoadhesive ocular formulation GT-NEKA demonstrated sol-gel transformation at physiological temperature, exhibited pseudoplastic flow behavior, and followed a Korsmeyer-Peppas release profile, and the cumulative amount of permeated vitamin A for 4 hours was (220.759?31.869) ?g.  GT-NEKA was found to be safe and non-irritating effect, showed the free radical scavenging activity of IC50 (9.367?0.021) mg/mL and the anti-inflammatory potential of IC50 (1.564?0.004) mg/mL. The analysis method for determining vitamin A levels using the HPLC instrument and UV-Vis Spectrophotometer has been successfully validated.

The mucoadhesive ocular formulation of GT-NEKA has been successfully developed. It is safe, non-irritating, and capable of releasing and delivering vitamin A to the corneal surface. Additionally, it shows potential in scavenging free radicals and providing anti-inflammatory effects, while also demonstrating stability during storage.

Kata Kunci : Cetalkonium klorida, Mukoadesif, Poloxamer, Sediaan Okular, Vitamin A