Effect of excipients and processing parameters on floating characteristics of hydrodynamically balanced system for diltiazem hydrochloride.

P.S. Salve*

Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus,

Mahatma Fuley Shaikshanik Parisar, Amravati Road, Nagpur – 440 033 (MS)

*Corresponding Author E-mail: pramodsalve77@yahoo.com

ABSTRACT:

The hydrodynamically balanced system (HBS) is based on the gel forming hydrocolloids which swells when comes in contact with water resulting in dosage form with density less than unity^10,11. The orientation of charged hydrophilic groups towards water results in HBS phenomenon. Hydrocolloids used are hydroxypropylmethyl cellulose derivatives. The present study deals with formulation of diltiazem HCl HBS. The effect of polymer viscosity, processing parameter on floating characteristics and drug release was studied. A direct compression method and 1:1 to 1:5 ratio of drug: HPMC K4M, K15M and K100M were used for development of HBS. The floating characteristic and in vitro drug release was studied in pH 1.2 buffer. The effect of hardness on floating behavior of HBS was studied. An increase in hardness resulted in non-floating dosage form. The HBS tablets containing 1:1 ratio of drug: polymer were found to be non-floating even at low hardness values. Hence, by varying the hardness, the floating characters can be obtained. In-vitro drug release profile reveals that increase in drug: HPMC ratio resulted in retardation of drug release.

KEYWORDS: The hydrodynamically balanced system, floating, hardness.

INTRODUCTION:

The hydrodynamically balanced system is based on the gel forming hydrocolloids which swells when comes in contact with water. The swollen matrix maintains the shape and posses a density of less than one within the outer gelatinous barrier as well entraps the air providing buoyancy to the dosage form. The sustained release characteristic is provided by the system since the drug molecules diffuse through the swollen matrix. The technology for the development of hydrodynamically balanced system involves intimate mixing of drug with the hydrocolloid such as hydroxypropylmethyl cellulose (HPMC) K4M, K15M, and K100M. The low density fatty acid materials are also used in the development of HBS. The advantage provided by these materials is the ability to control the drug release effectively as well as to provide buoyancy to the dosage forms. Diltiazem HCl is the calcium channel blocker used as anti-hypertensive agent. It has oral bioavailability of 38%. It shows selective absorption from upper part of small intestine. Its biological half-life is 4 hours. Hence hydrodynamically balanced system of Diltiazem HCl was developed using HPMC K4M, K15M and K100.

MATERIALS:

Diltiazem Hydrochloride (Zim Laboratories, Nagpur), Hydroxy propyl methyl cellulose (HPMC), K4M, K15M, and K100M (Colorcon Asia Pvt.Ltd., Goa), Talc (Zim Laboratories, Nagpur), Magnesium Stearate (Zim Laboratories, Nagpur), sodium chloride (S.D. Fine Chem. Ltd). All other chemicals and excipients were of analytical grade.

METHODS:

Development of hydronamically balanced system floating tablets

The formulation of diltiazem HBS formulation batches is shown in table 1, 2 and 3. The drug and polymer were passed through 40# sieve and mixed. To it magnesium stearate and talc were added and further mixed for 5 minutes. The tablets were compressed using 8 mm standard biconvex punches at a weight of 183 and 275 mg. The compression of the tablets for the weights of 366 to 549 mg as shown in table 1, 2 and 3 was done using 11 mm flat faced beveled edge punch on a single punch compression machine (Kilburn Manesty). The compression pressure was adjusted for the individual formulation batches for optimizing the floating characteristics.

Table 1 Formulation of diltiazem HCl HBS tablets containing HPMC K4M

Formulation code.Þ Ingredients (mg)ß	F1	F2	F3	F4	F5
Diltiazem HCl	90	90	90	90	90
HPMC K4M	90	180	270	360	450
Magnesium stearate	1	2	2	2.5	3
Talc	2	3	4	4.5	6
Tablet weight (mg)	183	275	366	457	549

Table 2 Formulation of diltiazem HCl HBS tablets containing HPMC K4M

Formulation code.Þ Ingredients (mg)ß	F1	F2	F3	F4	F5
Diltiazem HCl	90	90	90	90	90
HPMC K4M	90	180	270	360	450
Magnesium stearate	1	2	2	2.5	3
Talc	2	3	4	4.5	6
Tablet weight (mg)	183	275	366	457	549

Table 3 Formulation of diltiazem HCl HBS containing HPMC K15M

Formulation code.Þ Ingredients (mg)ß	F11	F12	F13	F14	F15
Diltiazem HCl	90	90	90	90	90
HPMC K100M	90	180	270	360	450
Magnesium stearate	1	2	2	2.5	3
Talc	2	3	4	4.5	6
Tablet weight (mg)	183	275	366	457	549

Physical Evaluation of HBS Tablets

HBS tablets were evaluated for mechanical strength using Monsanto hardness tester and friability using Roche friability test apparatus. The buoyancy test was carried in pH 1.2 buffer and the time required for the tablet to float on the surface was determined.

Drug Content

Five tablets were weighed and powdered. The quantity of powder blend equivalent to 90 mg of diltiazem HCl was weighed accurately and taken in 100 ml volumetric flask. To it 50 ml of pH 1.2 buffer was added and sonicated for 5 minutes. The volume was made upto 100 ml with pH 1.2 buffer and filtered. From the above solution, 2 ml was diluted to 100 ml. The drug content was determined spectrophotometrically at 238 nm.

In vitro dissolution studies

Formulation Code	Hardness	Floating status
F1	2 kg/cm^2	Non-floating, up and down movement in buoyancy test in pH 1.2 buffer
F2	2 kg/cm^2	Floating
F3	27 Nm^2	Floating
F4	33 Nm^2	Floating
F5	35 Nm^2	Floating
F6	2 kg/cm^2	Floating
F7	2 kg/cm^2	Floating
F8	27 Nm^2	Floating
F9	33 Nm^2	Floating
F10	35 Nm^2	Floating
F11	2 kg/cm^2	Floating
F12	2 kg/cm^2	Floating
F13	23 Nm^2	Floating
F14	23 Nm^2	Floating
F15	35 Nm^2	Floating

The in vitro dissolution studies were carried in 900 ml pH 1.2 buffer using USP type II dissolution test apparatus at 75 rpm at 37±0.5 ⁰C. After regular time intervals, a specified volume was withdrawn and replaced with dissolution medium. The withdrawn samples were analyzed spectrophotometrically at 238 nm using pH 1.2 buffer as blank.

RESULTS AND DISCUSSION:

Effect of hardness on floating characteristic of diltiazem HCl HBS tablets

The optimum hardness for the formulation batches is shown in table 4.

Table 4 Optimum hardness values for floating characteristic of diltiazem HCl HBS tablets

The increase in the hardness in the formulation batches F1, F2, F6, F7, F11 and F12 from 2 kg/cm² to 2.5-3 kg/cm² resulted in the non-floating characteristics. Similarly, the increase in hardness of formulation batches F3, F4, F5, F8, F9, F10 from 27, 33 and 35 Nm² respectively to 28, 34, and 36 Nm² resulted in the non-floating characteristics of the dosage form.

In vitro dissolution studies

The in vitro dissolution profiles of diltiazem HCl HBS tablets containing HPMC K4M, K15M and K100M are shown in figure 1, 2 and 3 respectively. The increase in ratio of drug: HPMC K4M from 1:1 to 1:5 retarded the drug release proportionately from 77.322 to 38.19% in 8 hours of dissolution studies. The formulation batch containing drug: HPMC K4M in 1:1 ratio resulted in non-floating dosage form. The formulation batches containing HPMC K15M in 1:1 to 1:5 ratios were found to be floating and the drug release was retarded from 68.52 to 44.32 % in 8 hours. The formulation batches containing HPMC K100M from 1:1 to 1:5 ratios retarded the drug release from 73.51 to 41.10 %.

Figure 1 Dissolution profile of diltiazem HCl HBS tablets containing HPMC K4M

Figure 2 Dissolution profiles of diltiazem HCl HBS tablets containing HPMC K15M

Figure 3 Dissolution profile of diltiazem HCl HBS tablets containing HPMC K100M

REFERENCES:

1. Ali J, Arora S, Ahuja A, Babbar AK, Sharma RK, Khar RK, Baboota S. Formulation and development of hydrodynamically balanced system for metformin: In vitro and in vivo evaluation, Eur. J. Pharm. Biopharm. 67 (2007) 196–201.

2. T. Bussemer, A. Dashevsky and R. Bodmeier, A pulsatile drug delivery system based on rupturable coated hard gelatin capsules. I. Control. Release Vol. 98 (1) (2004) 75-85.

3. A. Streubel, J. Siepmann and R. Bodmeier. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release. Eup. J. Pharm. Sci. Vol. 18, Issue 1 (2003) 37-45.

4. A. Streubel, J. Siepmann and R. Bodmeie, Floating microparticles based on low density foam powder. Int. J. Pharm. Vol. 241, Issue 2 (2002) 279-239.

5. M. Rosa J. Castellanos, H. Zia, C. T. Rhodes, Design and testing in vitro of a bioadhesive and floating drug delivery system for oral application. Int. J. Pharm. 121, (1) (1995) 37-44.

6. P. Dorożyński, P. Kulinowski, R. Jachowicz, A. Jasiński, Development of a system for Simultaneous dissolution studies and magnetic resonance imaging of water transport in hydrodynamically balanced systems: A technical note. AAPS PharmSciTech; 8 (1) Article 15 (2007) E1-E4.

7. T. Bussemer, A. Dashevsky, R. Bodmeier. A pulsatile drug delivery system based on rupturable coated hard gelatin capsules. J. Control. Release 93 (3) (2003) 331-339.

8. Indian Pharmacopeia, volume I, Controller of Publication, Delhi, 1996, PP. 256.

9. D.M. Kerins, R.M. Robertson, D. Roertson, Drugs used for treatment of myocardial ischemia, in: J.G. Harman, L.E. Limbird (Eds.), Goodman and Gilman’s The Pharmacological basis of therapeutics, Tenth Edition, Mc-Graw-Hill, 855-860, 1949.

10. P.R. Sheth, J.L. Tossounian, Novel sustained release tablet formulations, US Patent 4, 167, 558, September 11, 1979.

11. P.R. Sheth, J.L. Tossounian, The hydrodynamically balanced system (HBSE): a novel drug delivery system for oral use, Drug Dev. Ind. Pharm. 10 (1984) 313-339.

12. Hand book of pharmaceutical excipients, R.C. Rowe, P.J. Sheskey, S.C. Owen (Ed.) third edition, American Pharmaceutical Association, Washington, D.C.

Received on 22.09.2011 Accepted on 28.09.2011

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Asian J. Res. Pharm. Sci. 1(4): Oct.-Dec. 2011; Page 97-99