Characterization and Optimization of Capryol-90, Polysorbate-80, And Peg-400 Proportion in Mefenamic Acid Self Nanoemulsifying Drug Delivery System (SNEDDS) With Simplex-Lattice-Design

Abstract

Mefenamic acid as pain relief drug belongs to the biopharmaceutics classification system (BCS) class II which is practically insoluble in water causing extremely low dissolution in gastrointestinal tract. The self nanoemulsifying drug delivery system (SNEDDS) is a new innovation pharmaceutical dosage form that has effectively known to increase solubilization of hydrophobic drug in polar solvent. In this study the capryol-90 was selected as oil phase in SNEDDS as it showed maximal solubility of mefenamic acid (20 mg/mL). Combination of polysorbate-80 and PEG-400 as a generally regarded as safe (GRAS) excipient were used as surfactant and co-surfactant in SNEDDS due to its high HLB property that can increase mefenamic acid solubility in water. The ternary phase diagram of capryol-90, polysorbate-80, and PEG-400 was constructed in advance to obtain the component concentration of spontaneous nanoemulsion region. Model simplex-lattice-design cooperated in Design-Expert®10 was used to define SNEDDS mefenamic acid formula. Optimized mefenamic acid SNEDDS formula consisted of 20% capryol-90, 31.62% polysorbate-80, and 48.38% PEG-400. Characterization study of Optimized mefenamic acid SNEDDS formula showed improvement of drug content (102.820 ± 4.950)%, emulsification time (421.015 ± 1.290) second, and viscosity (0.927 ± 0.017) mm2/s 30oC. One way ANOVA statistical analysis result of optimal formula SNEDDS (105.210 ± 4.425)% of drug content, commercial generic caplet (0.917 ± 0.094)%, and mefenamic acid powder capsule (10.446 ± 0,333)% gave significant value (sig*) below than 0.05. Optimal formula proved that SNEDDS can significantly increase mefenamic acid dissolution of pH 7.4 (ileum fluid). The optimal formula of mefenamic acid SNEDDS successfully formed an uniformity droplet size (PDI 0.18) with mean size 241.9 nm and the surface charge has a value of -16.5 mV respectively.

Solid Self Nano Emulsifying Drug Delivery System (Solid Snedds) of Mefenamic Acid: Formula Optimization Using Aerosil®-200 and Avicel® Ph-101 With Factorial Design

“…In the final stage, polysorbate-80 was added and the mixture was sonicated with a bath sonicator briefly to obtain a clear yellow solution. Amount of each component follow the result of previous study conducted by Mardiyanto et al 6 .…”

“…Despite its clinical importance, long term use mefenamic acid is limited due to the gastrointestinal side effect it exerted, which leads to the importance on alternative strategies to reduce the dose while maintaining similar clinical outcome 5 . Research conducted by Mardiyanto et al 6 indicate conclusive results of SNEDDS comprised of capryol-90, polysorbate-80, and polyethylene glycol (PEG) 400 was able to significantly increase the dissolution of mefenamic acid compared to marketed tablets SNEDDS have been developed into solid SNEDDS to mitigate problems of SNEDDS such as stability and ease of administration (acceptability for patients). Solid SNEDDS is a solidification of SNEDDS system by using a certain porous carrier [7][8][9] .…”

Artikel Review: Optimasi Formulasi Snedds Dengan Simplex Lattice Design Dan Box Behnken Design

“…Beberapa fase minyak yang digunakan dalam formulasi SNEDDS meliputi capryol PGMC, minyak biji jintan hitam, asam oleat, minyak kelapa/VCO, capryol-90, olive oil, capryol-90, peceol, kombinasi peceol dan etiloleat, capmul MCM dan cremophor EL. [5][6][7][8][9][10][11]14,22,23 Suatu Surfaktan dapat menghasilkan nanoemulsi tipe minyak dalam air apabila memiliki HLB>10. 24 Surfaktan yang terlokalisasi pada droplet emulsi dapat menurunkan energi bebas antar muka dan menghasilkan barier terhadap koalesensi sehingga terjadi dispersi spontan secara termodinamika.…”

“…Optimasi formulasi SNEDDS dapat menggunakan metode simplex lattice design dan box behnken design. [5][6][7][8][9][10][11][12][13][14] Pengembangan formulasi SNEDDS dapat meningkatkan bioavailabilitas oral, kelarutan dan permeabilitas intestinal. 15 Simplex lattice design (SLD) merupakan desain campuran dalam optimasi formulasi dengan syarat jumlah total bahan-bahan yang digunakan dalam formulasi selalu konstan.…”

“…8,16 Metode SLD memungkinkan jumlah eksperimen optimasi formulasi yang sedikit. [8][9][10][11] Desain eksperimen lain yang dapat digunakan untuk optimasi formulasi SNEDDS adalah box behnken design (BBD) yang memiliki keunggulan dibandingkan desain penuh tiga level faktorial dan composite central design (CCD) karena lebih efisien dengan jumlah variabel yang sama namun jumlah percobaan yang dilakukan lebih sedikit sehingga dapat mereduksi biaya uji. 17 Pemanfaatan SLD dan BBD dalam optimasi formulasi meminimalkan jumlah percobaan dalam memperoleh formulasi SNEDDS yang optimal sehingga dapat menghemat biaya.…”