Short Communication

2019  |  Vol: 4(2)  |  Issue: 2(March-April) | https://doi.org/10.31024/apj.2019.4.2.4

Preparation, characterization and in vitro evaluation of Osmotic-controlled release Isosorbide-5-mononitrate tablets

Sanjay Kumar Yadav*, Arti Gupta, Amrit Patel, Ravinder Bhati

IIMT College of Pharmacy, Greater Noida, Uttar Pradesh, India

*Address for Corresponding Author

Prof. Sanjay Kumar Yadav

IIMT College of Pharmacy, Greater Noida, Uttar Pradesh, India

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Abstract

Objective: Isosorbide Mononitrate is mainly indicated for the treatment of stable and unstable angina pectoris, acute myocardial infarction and heart failure. The objective of the present study was to develop sustained release tablet of Isosorbide Mononitrate by porous membrane osmotic technology. Material and methods: The tablets were prepared by wet granulation method. The granules were evaluated for angle of repose, bulk density, tapped density, compressibility index and Hausner ratio. The tablets were subjected to thickness, hardness, friability, weight variations, and drug content by assay and in vitro dissolution studies. The drug release from Isosorbide Mononitrate sustained release was carried out in 1.2N HCl, 4.5 pH acetate buffer and 6.8 pH phosphate buffer for 24hrs. Results and conclusion: The granules showed satisfactory flow properties, compressibility index and drug content. All the tablets formulations showed acceptable pharmaceutical properties. Formulation variables like type (PVP, PEG 4000 and HPMC) and level of pore former (0-55%, w/w of polymer), percent weight gain were found to affect the drug release from the developed formulations. The optimized formulation showed the highest f2 (f2 = 76.4) value. The drug release from the developed formulation was independent of pH and agitation intensity. The similarity factor f2 was applied between the optimized formulation and the theoretical dissolution profile.

Keywords: Coating, extended release, Isosorbide mononitrate, osmotic pressure, osmotic pump, stability

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Introduction

The aim of the work is to investigate the possibility of obtaining a prolonged, relatively constant level of isosorbide-5-mononitrate.Isosorbide -5-Mononitrate has long elimination half-life of 4-5 hours in comparison of isosorbide Di-nitrate. Despite of this long elimination half-life, Isosorbide Mononitrate is prescribed 2-3 times/day for prophylactic treatment of angina leads to poor patient complaints and development of tolerance (Lordi, 1991). Present studies investigate the possibility for the development of sustained release tablet of ISMN, to reduce the side effect, dosing frequency and improve patient compliance. Keeping these factors in view it is aim to formulate and evaluate SR tablet of 20 mg, to provide a controlled and predictable release of isososrbide-5-mononitrate, which is an organic nitrate used as anti-anginal drug for the treatment of stable and unstable angina pectoris, acute myocardial  infarction for once daily administration (Kumar and Sharma, 1991).  The present study, aim towards the development of sustained release of drug from the tablet by using osmotic technology. Theoretically design zero – order delivery pattern for the release the drug from the formulation. Considering different formulation variables and the selection of the optimized formulation from the drug release profile, considering the cost of drug by reducing the drug dose and increasing its effectiveness and deliver drug at near constant rate.

Material and methods

Preparation of Osmotically Controlled Sustained release tablets

Core tablets of Isosorbide Mononitrate were prepared by wet granulation method (Santus and Baker, 1995; Okimoto et al., 1999). The formulation is composed of lactose as diluents, sodium chloride as osmogent, PVP dissolved in isopropyl alcohol as granulating agent. Magnesium stearate and silicon dioxide were finally added as glident and lubricant. All the powders were passed through 30 mesh sieve. In the formulation of core tablet Isosorbide Mononitrate and Lactose were mixed for few minutes. Then powdered Sodium chloride was added and continued mixing for 5 minutes. To the power mixture PVP dissolved in Isopropyl alcohol were added as granulating agents and continued mixing for 10 minutes. To the mix, magnesium stearate and colloidal silicon dioxide were added and mixed for 10 minutes. The granules formed were coated with eudragit dissolved in Isopropyl alcohol coating solution and are dried. Then the granules were compressed to round tablet having an average weight of 150 mg using a multi-stroke tablet punching machine. The core tablets of Isosorbide Mononitrate were coated in standard coating pan. The composition of coating solution includes HPMC, PVP, PEG 4000, Propylene Glycol and ethylene dichloride. The components were added in the solvent mixture in sequential manner. Core tablets were placed in the coating pan, rotated at a low speed of 15-20 rpm and heated air was passed through the tablet bed. Coating process started once the outlet temperature reached optimal. The coating solutions were sprayed at specific rate and maintained the inlet temperature at 45-50ºC.Then the coated tablets were dried at 50ºC before further evaluation. Composition of tablet formulations is given in table 1.

Table 1. Formulation of core tablets

S. N.	Ingredients	Quantity for 1 tablet (150 mg)
1	Isosorbide Mononitrate	20.00
2	Lactose	65.00
3	Sodium Chloride	35.00
4	PVP	10.00
5	Magnesium Stearate	2.00
6	Silicon dioxide	0.50
7	Eudragit	5.00
8	Isopropyl Alcohol	q.s

 

Table 2. Development of various tablet formulations

Ingredients	FI	F2	F3	F4	F5	F6	F7
Ethyl Cellulose	3.95	3.66	3.30	3.00	2.74	2.74	2.74
HPMC	-	-	-	-	-	1.52	-
PEG 4000	-	-	-	-	-	-	1.52
PVP	-	0.37	0.82	1.20	1.52	-	-
Propylene Glycol	1.05	0.98	0.88	0.80	0.73	0.73	0.73
Ethanol	38.00	38.00	38.00	38.00	38.00	38.00	38.00
Dichloro methane	57.00	57.00	57.00	57.00	57.00	57.00	57.00

Characterization of tablet formulation

The prepared tablets were characterized for the parameters such as weight variation, thickness and length using a Vernier Calipers, hardness test was performed using a Monsanto Hardness tester, friability test was performed using a Roche Friabilator, drug content by UV Spectrophotomertic method.

Results and discussion

Pre formulation observations

The preformulation observation of powdered was mainly with respect to color, taste and odor that was found as white to off - white powder, with bitter taste and odorless.

Characterization of powder granules and formulations

Angle of repose was determined as per standard method. The angle of repose average was found as 41.116°. Granules showed average angle of repose was 28.260°. The results of the tablet indicate that the granules ready for compression showing fair to good flow ability with the angle of repose values ranging from 27.86 to 28.53 according to the readings and are better than that of powder drug.

The results of bulk and tapped density of Isosorbide Mononitrate powder were observed as 0.360 and 0.484 (g/cm³), respectively. In case of granules, average bulk density and tapped density of Isosorbide Mononitrate granules were observed as 0.764 and 0.804 g/cm³, respectively.

The results of powder compressibility for Isosorbide Mononitrate bulk powder and granules were found as 4.82 and 5.62, respectively. The Hausner Ratio of Isosorbide Mononitrate bulk powder and granules were found as 1.02, and 1.08, respectively.

The dissolution profile of all formulation was given in figure 1. Table 3 showed observations of all characterization parameters for prepared tablets. Comparison of cumulative percent drug release of optimized formulation with marketed SR tablet is given in figure 2. Figure 3 showed cumulative percent drug release profile of optimized formulation on agitational intensity.

Figure 1. Dissolution profile of all formulation (F1-F7)

 

Table 3. Characterization of tablet formulations

Parameters	F1	F2	F3	F4	F5	F6	F7
Uniformity of weight	Pass	Pass	Pass	Pass	Pass	Pass	Pass
Hardness (Kg/cm2)	6.82	7.24	7.63	7.31	7.35	7.39	6.87
Thickness (mm)	3.52	3.53	3.56	3.62	3.58	3.52	3.66
Diameter (mm)	6.51	6.50	6.52	6.51	6.50	6.49	6.50
Friability (%)	0.01	0.01	0.01	0.01	0.01	0.01	0.01
Drug Content (%)	96.203	94.45	95.542	93.454	98.403	97.087	96.976

Figure 2. Comparison of Cumulative % Drug release of optimized formulation with marketed SR tablet (Monit SR)

 

Figure 3. Cumulative % Drug release profile of optimized formulation on agitational intensity

 

Discussion and conclusion

Sustained release tablets of Isosorbide Mononitrate were prepared by wet granulation technique. In vitro studies showed formulation F5 was well suited to be sustained release formulation. The coating solutions were prepared by using various polymers and pore formers, meets all the ideal characteristics to formulate in the form of sustained release drug delivery system. Under pre formulation study, the organoleptic properties were complied with the BP specification. Physical properties such as bulk density and tapped density were more in case of granules ready for compression than that of Isosorbide-5 Mononitrate raw powder. The compatibility evaluation was performed by FT-IR spectroscopy analysis. The study implies that the drug and polymers were compatible with each other. There were no interactions found between the drug and the polymers.F5 formulation was optimized as it complied with all the pharmacopoeial specifications. The physical parameters like thickness, diameter, hardness, friability, weight variations were carried out. The assay was carried out for optimized formulation and the result was found to be 98.403%.  The drug release from the developed formulations was independent of pH and agitational intensity of the release media. It was found that the drug release increases with increasing the level of pore former (PVP), the membrane became more porous after coming in contact with the aqueous environment.  The drug release was found to decrease with the increase in the weight gain of the membrane. The drug release was found to be more with PVP than with HPMC, Ethyl Cellulose and PEG4000. The similarity factor f2 was applied between the dissolution profile of optimized batch and the theoretical dissolution profile, which also indicate a decent similarity between both dissolution profiles. Stability studies were carried out by keeping the Sustained release tablets at room temperature (25ºC ± 2ºC/ 60% ± 5% RH) and at accelerated temperature (40ºC ± 2ºC/ 75% ± 5% RH) in stability chamber for 60 days. The result of stability studies conducted on F5 revealed no change in physical appearance, drug content and in vitro dissolution profile, hence F5 formulation was found to be stable at tested temperature.

Conflicts of interest: Not declared.

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