PHARMACOKINETIC AND PHARMACODYNAMIC OF MATRIX-TYPE PATCHES CONTAINING IBUPROFEN

• Main Author: Siska Anastasia, Desy
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45762
• Institution: Institut Teknologi Bandung

Ibuprofen is an anti-inflammatory drug with short half life that can cause adverse effects, such as gastrointestinal tract ulcers when administered orally. Topical ibuprofen as an alternative dosage form could be promising in minimizing the adverse effects and in the same time might prolong duration of the drug through a controlled release delivery system. Matrix type of transdermal patch can reduce the dose dumping, which lead to reduce the adverse effects when compared to orally administered ibuprofen. In this current study, ibuprofen patch was prepared in 5 cm diameter (225 mg/patch) by mixing ibuprofen in HPMC matrix (9%) with propylene glycol was added as a plasticizer. Mechanical evaluation of ibuprofen patch showed tensile strength of 1.24 ± 0.14 kg/mm 2 , % elongation of 61.31 ± 8.61, folding endurance of more than 200 times and water content of 1.50 ± 0.28 %. In vitro release was performed for 36 h using flow-through diffusion cells and Python reticulatus shed snake skin was used as a membrane. Cummulative diffusion percentage of ibuprofen was 78.84 ± 0.84 % with drug permeation kinetics followed Higuchi models. The irritation test performed in rabbits showed that the patch caused neither erythema nor edema. Pharmacokinetic evaluation was performed in male Wistar rats which divided into 2 groups (n=5 for each group), i.e. the first group was given ibuprofen orally (62 mg/kg BW) and the second was given ibuprofen patch (124 mg/kg BW). Cmax and AUC0-24 ibuprofen from oral administration (90.82 ± 4.77 µg/mL and 242.91 ± 19.76 µg.h/mL) were significantly different (p<0.05) from transdermal administration (3.61 ± 3.12 µg/mL and 55.22 ± 4.44 µg.h/mL). Tmax from oral administration was 0.25 h, while transdermal ibuprofen patch achieved relatively constant plasma concentrations (2-4 µg/mL) started at 0.5 up to 24 h. The pharmacodynamics evaluation was carried out by monitoring an antiinflammatory effect of ibuprofen patch in lambda carrageenan (1% solution) induced paw edema rats. Test animals were divided into 2 groups (n=5 for each group). The first group was the control group (without administered drug) and the second group was given transdermal ibuprofen patch (124 mg / kg BW). Percent inflammation was significantly different in ibuprofen patch group (p <0.05) with % inflammation was reduced up to 72% in 10 h. Therefore, it could be concluded that ibuprofen patch produced a relatively contant release up to 24 h and showed an anti-inflammatory activity with plasma concentrations were much lower than those achieved from oral administration.