FORMULASI DAN OPTIMASI TABLET FLOATING SALBUTAMOL SULFAT MENGGUNAKAN FACTORIAL DESIGN

Wa Ode Sitti Zubaydah, S.Si., Prof. Dr. Achmad Fudholi, DEA, Apt.

2012 | Tesis | S2 Ilmu Farmasi

Salbutamol sulfat memiliki waktu paruh eliminasi yang relatif pendek (4 jam), dengan dosis per oral 2-4 mg, dan pemberian 3-4 kali sehari. Formulasi salbutamol sulfat dalam sediaan tablet lepas lambat diharapkan dapat mengurangi frekuensi pemakaian obat, menghasilkan konsentrasi salbutamol sulfat dalam darah yang lebih seragam dan kadar puncak yang tidak fluktuatif. Sifat fisik tablet dan pelepasan obat dari tablet sistem floating dipengaruhi oleh sifat komponen penyusun matrik yaitu: Etil Selulosa (matrik hidrofobik), xanthan gum (free flowing, gelling agent), serta natrium bikarbonat yang akan bereaksi dengan cairan lambung membentuk CO2. Penelitian dilakukan dengan model factorial design dengan 3 komponen yaitu: etil selulosa (A), xanthan gum (B), dan natrium bikarbonat (C) sehingga didapatkan 8 rancangan formula. Keseragaman kandungan, floating lag time, kinetika pelepasan obat orde pertama (K orde 1), dan nilai DE360 salbutamol sulfat digunakan sebagai parameter optimasi. Berdasarkan model factorial design, didapatkan persamaan dan contour plot untuk masing–masing parameter tersebut, sehingga formula optimum dapat ditentukan. Etil selulosa memberi pengaruh dominan terhadap keseragaman kandungan. Natrium bikarbonat merupakan faktor yang berpengaruh sangat dominan terhadap floating lag time. Komponen etil selulosa dan xanthan gum meningkatkan nilai K orde 1, sedangkan natrium bikarbonat memperkecil nilai K orde 1. Natrium bikarbonat paling berpengaruh dalam memperkecil nilai DE360. Berdasarkan pendekatan nilai desirability didapatkan formula optimum teoritis dengan komposisi etil selulosa 17,58 mg, xanthan gum 78,51 mg, dan natrium bikarbonat 30 mg

Salbutamol sulphate has a relatively short half-life (4 hours), with oral doses of 2-4 mg, with 3-4 times daily administration. Sustained-release formulation of salbutamol sulphate in a tablet dosage form is expected to reduce the frequency of drug use, produce more uniform serum concentrations with less fluctuation in peak through levels. The physical properties of tablets and drug release from tablets floating system are influenced by properties of matrix component, i.e. Ethyl cellulose (hydrophobic matrix), xanthan gum (free flowing, gelling agent), and sodium bicarbonate that reacts with gastric fluid to form CO2. The research was done with factorial design by using 3 components, i.e. ethyl cellulose (A), xanthan gum (B), and sodium bicarbonate (C), so that eight formula were obtained. The Optimization parameters of salbutamol sulphate sustained-release were drug content uniformity, floating lag time, first order kinetics of drug release (K of first order), and the DE360. Based on factorial design model, equations and contour plots were obtained, by which the optimum formula can be determined. Ethyl cellulose was the most dominant factor in increasing uniformity of content. Sodium bicarbonate is the dominant factor affecting to the floating lag time. Ethyl cellulose and xanthan gum increase the value of K-first order, while sodium bicarbonate is decrease it. Sodium bicarbonate is the most influential in reducing the DE360. Based on desirability value, optimum formula 17.58 mg of ethyl cellulose, 78.51 mg of xanthan gum, and 30 mg of sodium bicarbonate were obtained.

Kata Kunci : salbutamol sulfat, tablet floating, etil selulosa, xanthan gum.