Release of Ibuprofen from Stearic Acid Based fusion Matrix
1Goupale DC*, 1Ghode P, 1Mehta K and 2Dhongade H
1Siddhant College of Pharmacy, Talegaon-Chakan Road, Sudumbare, Dist Pune 412 109
2J. L. Chaturvedi College of Pharmacy, Nagpur
*Corresponding Author E-mail: wdamu@rediffmail.com
ABSTRACT
The aim of the present study was to investigate the release of Ibuprofen (IB) from Stearic acid (SA) fusion matrix in different pH environments. The drug, Ibuprofen was added in weakly acidic waxy material i.e. stearic acid. This mixture was melted and re-solidified to get hard solid matrix. The results showed that the matrix has poor release (1%) in acidic medium (pH 1.3), 3% release in pH 3.6 and 12% release in pH 7.2 after 4 hrs. On other hand in basic medium (at pH 10.2) the matrix has complete release 99.97% within 30 minutes. The stearic acid fusion matrix significantly decreased the rate of drug release as the pH decreases of the dissolution medium. This fact may be implemented to develop colon specific (Basic environmental) drug delivery for drug those are gastric irritant.
KEYWORDS: Release, fusion matrix, Ibuprofen
INTRODUCTION:
So far, it has been reported that many different types of controlled-release dosage forms have been developed to improve clinical efficacy of drug and patient compliance1,2. A number of methods and approaches have been used in their formulation and are well reviewed3. The term fusion matrix describes a solid in which the drug is fused (Melted and solidified) in a skeleton of material and it can be molded in any predetermined size and shape. It is one of the least complicated approaches to manufacture sustained release or site specific dosage form that consists of a drug dispersed in a polymer, the polymer playing the role of a matrix 4-7. The matrix tablet, which incorporates the active ingredient in an inert material matrix, has been well known to act as an effective release medicament 8. It was found that the choice of matrix material, amount of drug incorporated in matrix, the hardness of the tablet, density variation and tablet shape could markedly affect the release rate of drug 9. Several other workers 10-14also reported that the rate of drug release from matrix is affected by the composition of the matrix, shape, pH of dissolution fluid, drug solubility, external agitation, amount of drug and the porosity of the matrix. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually good candidates for the development of colon specific release formulations. Ibuprofen, a prominent NSAID was selected in this experiment. It possesses analgesic, anü-inflammatory and anti-pyretic activities. Chemically Ibuprofen is 2-(p-isobutylphenyl) propionic acid, bearing the molecular formula C13H1802 Ibuprofen is indicated for symptomatic relief of rheumatoid arthritis and osteoarthritis. Its most frequent adverse effects are gastrointestinal disturbances e.g., GI ulcer and bleeding.
This drug is readily absorbed orally and plasma peak levels are reached within 2 h of administration. The elimination of Ibuprofen from plasma is first order with apparent half-life of 1.4 to 2.5 h. As Ibuprofen causes gastric irritation, GI ulcers, the objective of this study was to release the drug in intestine region bypassing gastric region.
MATERIALS AND METHODS:
Materials:
Ibuprofen (IB) was supplied as a gift sample by Lupin Limited, Mumbai, Stearic acid (SA) was procured from Research –Lab Fine Chem Industries, Mumbai. All other chemicals or reagents were of analytical grade. Electrolab tablet Dissolution tester. U.S.P. (XXI), Type 1 was used for dissolution studies. The samples were analyzed using a double beam spectrophotometer (UV-2203, Systronics).
Preparation of fusion Matrix:
Ibuprofen was mixed with stearic acid in the concentration containing 5%, 10% and 15 % w/w of drug in different containers. The mixture was heated to 75oC and stirred well to get homogeneous molten mass. It was transferred in cylindrical mould (1.0 cm, diameter) made of butter paper and it was allowed to solidify by natural cooling. A long cylindrical matrix was obtained that was further cut into few pieces with 1 g size each. The Matrix formulations obtained were labeled as
M5- Matrix containing 5% w/w Ibuprofen
M10- Matrix containing 10% w/w Ibuprofen
M15- Matrix containing 15% w/w Ibuprofen
Dissolution studies:
The dissolution studies were carried out using Dissolution Tester USP (XXI) taking one liter of buffer solution. The release of drug was studied in three different dissolution mediums (pH 1.3, 3.6 and 10.2).
Table 1: Release of Ibuprofen in different dissolution media from Stearic acid fusion matrix with respect to time
|
Sr. No. |
Time (Minutes) |
% Release in pH 1.3 |
% Release in pH 3.6 |
% Release in pH 10.2 |
||||||
|
M 5 |
M 10 |
M 15 |
M 5 |
M 10 |
M 15 |
M 5 |
M 10 |
M 15 |
||
|
1 |
10 |
0.00 |
0.01 |
0.09 |
0.51 |
0.48 |
0.55 |
36.47 |
34.3 |
38.81 |
|
2 |
20 |
0.01 |
0.14 |
0.27 |
1.20 |
0.64 |
0.97 |
68.61 |
71.2 |
73.79 |
|
3 |
30 |
0.13 |
0.19 |
0.37 |
1.82 |
1.67 |
1.36 |
99.97 |
98.3 |
99.2 |
|
4 |
60 |
0.15 |
0.27 |
0.39 |
2.60 |
2.5 |
2.57 |
99.97 |
98.3 |
99.2 |
|
5 |
90 |
0.16 |
0.36 |
0.52 |
3.73 |
3.14 |
2.9 |
99.97 |
98.3 |
99.2 |
|
6 |
120 |
0.24 |
0.49 |
0.65 |
4.50 |
4.67 |
3.89 |
99.97 |
98.3 |
99.2 |
|
7 |
150 |
0.35 |
0.53 |
0.72 |
5.77 |
5.99 |
4.67 |
99.97 |
98.3 |
99.2 |
|
8 |
180 |
0.52 |
0.69 |
0.87 |
6.32 |
6.57 |
5.92 |
99.97 |
98.3 |
99.2 |
|
9 |
210 |
0.80 |
0.83 |
0.96 |
6.90 |
7.84 |
6.81 |
99.97 |
98.3 |
99.2 |
|
10 |
240 |
1.00 |
1.12 |
1.24 |
7.95 |
8.31 |
7.34 |
99.97 |
98.3 |
99.2 |
Fig 1: Plot of Release of Ibuprofen from M 5 in different dissolution media from Stearic acid fusion matrix with respect to time
The temperature of dissolution medium was set at 37°C and paddle rotation was set at 100 rpm. Time was recorded as soon as the matrix formulations were put into the dissolution vessels. Five ml sample was withdrawn from each vessel at appropriate time intervals (10, 20, 30, 60, 90, 120, 150, 180, 210, 240 minutes) for the analysis of drug content. The same amount of fresh phosphate buffer was added immediately to the dissolution medium to compensate the volume.
Analysis of drug content:
The extent of release of IB from each matrix was measured at 221 nm wavelength using Systronics UV-2203 spectrophotometer. The corresponding buffers were used as blank. The absorbance data was processed and consequently the percent releases of the drug at different time intervals were obtained.
RESULTS AND DISCUSSION:
The results showed that with the increase in pH of the dissolution medium the release of dug increases from the stearic acid fusion matrix. The percentage release in different pH conditions with respect to time is shown in Table 1. The matrix containing 5%, 10% and 15% w/w were individually analyzed for dissolution. Independent of initial drug content in the matrix, the release was about 1% and 3% in pH 1.3 and 3.6 respectively after 4 hr. At the same time in pH 10.2, the release from M5 was found to be 99.97 % within 30 minutes. The results were more or less similar in M10 and M15. The graphically representation of drug release from M5 is shown in Fig 1.
CONCLUSION:
The results revealed that stearic acid matrix due to its insolubility in acidic pH do not release the drug in the same. This matrix may remain intact in gastric region (pH 1 to 3) and further it would pass to intestinal region (pH 8 to 10), releasing the drug. The study may be further subjected to in-vivo study and if the data permits this formulation could be used for colon specific delivery of drugs which are not suitable for gastric delivery.
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Received on 04.02.2009 Modified on 12.05.2009
Accepted on 22.07.2009 © RJPT All right reserved
Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 601-602