Process Optimization and Evaluation of Immediate Release Tablet containing Benzimidazoles
N. Sudarshan Rao*, Budda Leena
1Department of Pharmaceutics, Pulipati Prasad College of Pharmaceutical Sciences, Telangana, India.
2Department of Pharmacology, Browns College of Pharmacy, Telangana, India.
*Corresponding Author E-mail: kanneaboinak3@gmail.com
ABSTRACT:
Olmesartan is an angiotensin II antagonist used in the treatment of hypertension. In present investigation an attempt was made to develop solid oral formulation of Olmesartan. The purpose of this study was to develop the formulation as immediate release tablet of Olmesartan by using excipients by design of experiment. Tablets were prepared by using direct compression method. In HPLC study of Olmesartan the correlation coefficient was found to be 0.993 at 296 nm at flow rate of 0.7 ml/min at injection volume of 5 L Tablets were evaluated for hardness, thickness, dissolution calibration study, drug content and all the in-vitro studies were performed using USP apparatus type II All in-vitro studies were carried out using Phosphate buffer at 37°C ± 0.5°C. The optimized formulation showed in- vitro drug release of 96. 80 % at the end of 60 min. Comparing to other ARB’s drug shows high affinity Angiotensin II type 1 (AT1) receptors has long duration of action. Olmesartan has longest half life of 24 hrs where, T max is 0.5 – 1 hr, and it was so rapidly achieving desired plasma concentrations. Stability studies were carried out according to ICH guidelines. All the results were obtained within given ICH limits.
KEYWORDS: Olmesartan, in- vitro, UV calibration, HPLC parameters, Povidone k-25, crospovidone, ARB- (angiotensin receptor blocker).
INTRODUCTION:
Olmesartan is used to treat high blood pressure (hypertension) by blocking the hormone angiotensin thereby relaxing blood vessels, causing them to widen. High blood pressure reduction helps prevent strokes, heart attacks, and kidney problems. Olmesartan is an Angiotensin Receptor Blocker (ARB) shows high affinity for the angiotensin II type 1 (AT1) receptors, has a long duration of action, and has the longest half-life of any ARB (24hours).
It is indicated for the treatment of hypertension but Olmesartan’s dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD)1. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base. Pharmaceutical products designed for oral delivery and currently available on the prescription and over-the-counter markets are mostly the immediate release type, which are designed for immediate release of drug for rapid absorption. Disintegrating agents are substances routinely included in tablet formulations and in some hard shell capsule formulations to promote moisture penetration and dispersion of the matrix of the dosage form in dissolution fluids. Superdisintegrants improve disintegrant efficiency resulting in decreased use levels when compared to traditional disintegrants2. Traditionally, starch has been the disintegrant of choice in tablet formulation, and it is still widely used. For instance, starch generally has to be present at levels greater than 5% to adversely affect compatibility, especially in direct compression3. Drug release from a solid dosage form can be enhanced by addition of suitable disintegrants.
Mechanism of Disintegrants:
1) High swellability
2) Capillary action and high swellability
3) Chemical reaction
When introduced to an aqueous environment of use, the tablet rapidly takes up water, leading to swelling of the disintegrant and rapid disintegration of the tablet before the dispersion polymer can form a hydro gel. The disintegrant should be chosen such that it swells rapidly when introduced into the use environment and has a low tendency to form or promote formation of a hydrogel4. The rate of swelling of the disintegrant is directly correlated to tablet disintegration times. Tablets containing disintegrants cause more rapid swelling have faster disintegration times at comparable disintegrant levels5.
Table 1: materials used.
|
Sr. No. |
Materials |
Description |
|
1 |
API |
Alembic research centre, Baroda. |
|
2 |
Mannitol |
FMC Biopolymer, Shanghai, China. |
|
3 |
Povidone K-25 |
Medicine Health Product Company, China. |
|
4 |
Sodium Hydroxide |
Dow Chemicals, India. |
|
5 |
Meglumine |
Green Fine Chemical Co., Ltd. Shangai, China. |
|
6 |
Crospovidone (XL&XL-10) |
FMC Biopolymer, Shanghai, China. |
|
Sr. No. |
Concentration (μg/ml) |
Absorbance |
Avg. Absorbance Mean ± SD (n= 3) |
||
|
A1 |
A2 |
A3 |
|||
|
1 |
50 |
0.472 |
0.482 |
0.464 |
0.473±0.009 |
|
2 |
60 |
0.591 |
0.596 |
0.584 |
0.590±0.006 |
|
3 |
70 |
0.696 |
0.69 |
0.689 |
0.692±0.004 |
|
4 |
80 |
0.804 |
0.798 |
0.794 |
0.799±0.005 |
|
5 |
90 |
0.887 |
0.897 |
0.877 |
0.887±0.010 |
|
6 |
100 |
0.999 |
0.989 |
0.984 |
0.991±0.008 |
|
7 |
110 |
1.093 |
1.085 |
1.081 |
1.086±0.006 |
|
8 |
120 |
1.189 |
1.175 |
1.174 |
1.179±0.008 |
|
9 |
130 |
1.289 |
1.285 |
1.274 |
1.283±0.008 |
|
10 |
150 |
1.492 |
1.501 |
1.485 |
1.493±0.008 |
|
Equation y = 0.01x-0.014 |
|||||
Increasing Mg stearate concentration dissolution rate and extent decreases.
Replacing Mg stearate with sodium stearyl fumarate (SSF) dissolution rate and extent increases.
|
Ingredient |
Quantity/tablet(mg) |
|||
|
F1 |
F2 |
F3 |
F4 |
|
|
Intra granular part |
||||
|
Olmesartan |
80.00 |
80.00 |
80.00 |
80.00 |
|
Sodium hydroxide |
8.00 |
8.00 |
8.00 |
8.00 |
|
PovidoneK-25 |
15.00 |
15.00 |
15.00 |
15.00 |
|
Meglumine |
15.00 |
15.00 |
15.00 |
15.00 |
|
Mannitol |
277.00 |
286.00 |
278.00 |
270.00 |
|
Crospovidone (XL-10) |
25.00 |
16.00 |
24.00 |
32.00 |
|
Purified water |
Q.S |
Q.S |
Q.S |
Q.S |
|
Ethanol (96%) |
Q.S |
Q.S |
Q.S |
Q.S |
|
TOTAL |
420.00 |
420.00 |
420.00 |
420.00 |
|
Extra granular part |
||||
|
Mg stearate |
2.50 |
2.50 |
2.50 |
2.50 |
|
SSF |
10 |
10.00 |
10.00 |
10.00 |
|
Mannitol |
37.5 |
37.50 |
37.50 |
37.50 |
|
Crospovidone (XL) |
10 |
10.00 |
10.00 |
10.00 |
|
TOTAL |
480 |
480.00 |
480.00 |
480.00 |
|
Parameters |
Trial batches |
||
|
F2 |
F3 |
F4 |
|
|
Average Weight (mg) |
482.00 |
481.00 |
484.00 |
|
Thickness (mm) |
4.83 |
4.82 |
4.85 |
|
Hardness (kp) |
10-11 |
10-11 |
10-11 |
|
Friability (%w/w) |
0.059 |
0.02 |
NIL |
|
Disintegration time (min:sec) |
8:00-8:40 |
9:00-9:30 |
8:40-9:00 |
|
Drug content(%) |
98% |
100% |
99% |
Table 5: Result of In-vitro Release of Trial Batches F1-F4.
|
Trial batches |
F1 |
F2 |
F3 |
F4 |
|
TIME (min) |
%Drug released |
%Drug released |
% Drug released |
% Drug released |
|
10 |
35.00 |
29.20 |
40.00 |
35.60 |
|
15 |
72.00 |
65.00 |
73.00 |
68.00 |
|
20 |
91.70 |
80.00 |
85.00 |
83.00 |
|
30 |
96.80 |
95.80 |
97.90 |
95.00 |
|
45 |
98.70 |
99.10 |
99.80 |
95.60 |
|
60 |
99.80 |
99.70 |
100.1 |
96.90 |
Observation:
Dissolution of F2and F4 was found to slower than dissolution of B.NO: F3.
Increasing disintegrant intra granularly from16mg/tablet to 24mg/tablet show increase in dissolution.
Further increasing disintegrant to 32mg/tablet does not show improvement. So, intra granular disintegrant kept 24mg/tablet and trials to optimize extra granular disintegrant.
Table 6: Formula of Trial batches F5-F6.
|
Ingredient |
F5 |
F6 |
|
Quantity/tablet(mg) |
||
|
Intra granular part |
||
|
Olmesartan |
80.00 |
80.00 |
|
Sodium hydroxide |
8.00 |
8.00 |
|
PovidoneK-25 |
15.00 |
15.00 |
|
Meglumine |
15.00 |
15.00 |
|
Mannitol |
276.00 |
276.00 |
|
Crospovidone (XL-10) |
16.00 |
16.00 |
|
Purified water |
Q.S |
Q.S |
|
TOTAL |
410.00 |
410.00 |
|
Extra granular part |
||
|
SSF |
10.00 |
10.00 |
|
Mannitol |
36.00 |
28.00 |
|
Crospovidone (XL) |
24.00 |
32.00 |
|
TOTAL |
480.00 |
480.00 |
Table 7: Result of In-vitro Release of Trial Batches F5-F6.
|
Trial Batches |
F5 |
F6 |
|
Time (min) |
% Drug released |
% Drug released |
|
10 |
45.30 |
30.00 |
|
15 |
75.20 |
72.00 |
|
20 |
93.50 |
95.80 |
|
30 |
98.70 |
97.20 |
|
45 |
100 |
97.80 |
|
60 |
100.6 |
98.30 |
Olmesartan is a new Angiotensin II receptor antagonist. It is a BCS class-II drug and an antihypertensive drug which is used for the essential Hypertension only. It lowers systolic/diastolic blood pressure in patients with hypertension by up to 12/9mm Hg at 40mg and up to 13/10mm Hg at 80mg once daily. It gave better 24-hour control of blood pressure than amlodipine and losartan, particularly for the 18 to 24hour period after dosing when serum levels are lowest and the Risk of cardiovascular events is likely to be greatest. In present work immediate release tablet were prepared by using super-disintegrants like Crospovidone and other excipients. And prepared various formulations and carried out their Evaluation, we selected Crospovidone and Meglumine for its dissolution profile match with the innovator product. Reproducibility of the optimized formulation was checked and it was found that all the Parameters were reproducible and found satisfactory. The optimized immediate Release tablet was compared with the Innovator product and similarity factors were calculated. From the similarity factor and comparison with innovator product we can conclude that our Optimized formulation gives immediate release of drug for period of 1- hour which was found to be as significant as innovator product.
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Received on 25.02.2023 Modified on 19.04.2023
Accepted on 21.06.2023 ©Asian Pharma Press All Right Reserved
Asian J. Pharm. Ana. 2023; 13(3):180-182.
DOI: 10.52711/2231-5675.2023.00029