Formulation and In-Vitro Evaluation of Fast Dissolving / Disintegrating Tablets of Tizanidine Hydrochloride

Rahul K. Godge, Prakash N. Kendre, Mahendra A. Giri, Syed M. Zama, Syed N. Lateef*

Sanjivani College of Pharmaceutical Education and Research, Kopargaon Dist. Ahmadnagar.(M.S.) India.

ABSTRACT

Tizanidine hydrochloride, the first new oral treatment for muscle spasticity in the U.S. in more than 20 years. Fast dissolving tablets are solid dosage form that contains medicinal substances and that disintegrate and dissolve rapidly without water (within seconds) when placed on the tongue. Fast dissolving tablets of Tizanidine hydrochloride were prepared by direct compression method using Sodium Starch Glycolate, Ac-Di-Sol, and Indion 414 as a super disintegrants, and controlled tablets without any super disintegrant and evaluated for hardness, friability, disintegration time, dissolution time, water absorption ratio and content uniformity. All tablets containing super disintegrants shows release of drug more than 95% within 10 minutes and controlled tablet shows release of drug after 30 minutes. Tablets containing Indion 414 as a super disintegrant shows better result compare to others. Result also shows that as the concentration of superdisintegrant increases percentage release also increases.

KEY WORDS: Fast dissolving tablet, Direct compression, Tizanidine hydrochloride.

INTRODUCTION

An ideal dosage regimen in the drug therapy of any disease is one, which immediately attains the desire therapeutic concentration of drug in plasma or (at the site of action) and maintains it constant for the entire duration of treatment. Drugs are more frequently taken by oral rout. Although a few drugs taken orally are intended to be dissolved within the mouth, the vast majority of drugs taken orally are swallowed. Compared with alternate routes, the oral route of drug administration is the most popular and has been successfully used for conventional delivery of drug.

“Fast dissolving tablet is solid dosage form that contains medicinal substances and that disintegrates and dissolves rapidly without water (within seconds) when placed on the tongue.”¹ The Fast dissolving tablet is an important and attractive alternative to liquid dosage form.  Fast dissolving tablets are not only indicated for people having difficulty in swallowing but also ideal for unfavorable conditions of administration where water is not available. Syrups are best for pediatrics but they are bulky and drugs are not as stable in liquid form as in solid form like tablets,² when put on tongue, this tablet disintegrates instantaneously, releasing the drug, which dissolves or disperses in the saliva. Some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form. the disintegration time of these tablets depend largely on size and hardness parameters. ³

Tizanidine hydrochloride, the first new oral treatment for muscle spasticity in the U.S. in more than 20 years. ⁴ Tizanidine is used as a muscle relaxant (muscle relaxer) to treat muscle spasms, cramping, and increased muscle tone due to spasticity.

Name of Ingredients	Quantity in mg			Quantity in mg			Quantity in mg			Quantity in mg
	A1 1.5%	A2 2	A3 2.5%	B1 2%	B2 4%	B3 8%	C1 1%	C2 1.5%	C3 2%	Control
Tizanidine hydrochloride	2..22	2.22	2.22	2.22	2.22	2.22	2.22	2.22	2.22	2.22
Ac-Di-Sol	2.4	3.2	4	_	_	_	_	_	_	_
Sodium starch glycolate	_	_	_	3.2	6.4	12.8	_	_	_	_
Indion 414	_	_	_	_	_	_	1.6	2.4	3.2	_
D- mannitol	124.38	123.58	122.78	123.58	120.6	114.2	125.4	124.6	123.8	123
M.C.C	05	05	05	5	5	5	05	05	05	05
P.V.P	05	05	05	05	05	05	05	05	05	05
Aspartame	10	10	10	10	10	10	10	10	10	10
Magnesium stearate	05	05	05	05	05	05	05	05	05	05
Cab.O.Sil	05	05	05	05	05	05	05	05	05	05
Banana flavor	1	1	1	1	1	1	1	1	1	05
Total	160	160	160	160	160	160	160	160	160	160

Table No.1: Formulation of Drug using excipient

Table 2a: Powder Properties of Drug and excipient

S.No.	Parameters	Ac.Di.Sol			Sodium starch glycolate
		1.5	2	2.5	2	4	8
1	Angle of repose	26.054 ±0.0863	27.29 ± 1.070	26.877 ± 0.027	26.58 ± 1.703	26.405 ±1.342	26.202 ±1.053
2	Bulk density(g/cc)	0.3277 ± 0.005	0.3244 ± 0.0081	0.3277 ± 0.004	0.334 ± 0.003	0.3296 ± 0.0031	0.3315 ± 0.0083
3	Tapped density	0.3773 ± 0.0073	0.3898 ± 0.0115	0.3894± 0.004	0.3794 ± 0.0083	0.3978 ± 0.0045	0.3753± 0.014
4	Hauser ratio	1.151 ± 0.034	1.206 ± 0.032	1.188 ± 0.032	1.13 ± 0.021	1.205 ± 0.612	1.131 ± 0.0233
5	Percentage compressibility(g/cc)	13.146 ± 2.073	16.774 ± 2.28	15.809 ± 2.291	11.94 ± 1.895	17.03 ± 0.888	11.620 ± 1.808
6	Flowability	Excellent	Excellent	Excellent	Excellent	Excellent	Excellent

Table No.2 (b): Powder Properties of Drug and excipient

S.No.	Parameters	Indion 414			Control
		1	1.5	2
1	Angle of repose	27.22 ± 1.043	26.26 ± 2.66	27.056±0.030	27.226± 1.043
2	Bulk density(g/cc)	0.324 ± 0.003	0.331± 0.006	0.329± 0.006	0.3244 ± 0.008
3	Tapped density	0.357 ± 0.0064	0.377±0.0071	0.3594±0.009	0.3894± 0.0115
4	Hauser ratio	1.101 ± 0.222	1.138± 0.031	1.099 ± 0.187	1.206 ± 0.0321
5	Percentage compressibility(g/cc)	9.189 ± 1.83	12.138±2.369	9.143 ± 0.991	16.774 ± 2.288
6	Flowability	Excellent	Excellent	Excellent	Good

Table No.3 (a): Tableting properties of Drug and excipient

S.No.	Parameters	Ac-Di-Sol			Sodium starch Glycolate
		A1	A2	A3	B1	B2	B3
1	Weight variation ( ± %)	pass	pass	pass	pass	pass	pass
2	Hardness (Kg/cm^2)	2.03 ±0.057	2.1 ±0.1	2.16 ±0.05	2.03 ±0.057	2.1 ± 0.1	2.16 ±0.057
3	Friability (%)	0.557 ± 0.149	0.642 ±0.261	0.577 ±0.153	0.677 ±0.248	0.644 ±0.094	0.585 ±0.126
4	Disintegration time (sec)	59 ±1	57.33 ±2.08	56.33 ±2.51	58 ±2	56.33 ±1.14	54.33 ±1.52
5	Water absorption ratio	98.166 ±1.051	99.19 ±1.533	100.03 ±0.611	98.16 ±1.051	99.19 ±1.533	100.03 ±0.611
6	Uniformity of content (%)	pass	pass	pass	pass	pass	pass
7	Percentage release after 10 min (± %)	99.606 ±1.89	99.44 ±1.25	99.85 ± 0.73	99.90 ±0.72	100.05 ±0.63	100.48 ±0.78

Table No.3 (b): Tableting properties of Drug and Excipients

S.No	Ingredients	Indion			Control	Marketed
		C1	C2	C3
1	Weight variation (± %)	Pass	Pass	Pass	Pass	Pass
2	Hardness (Kg/cm^2)	2.03 ±0.058	2.1 ±0.1	2.167 ±0.058	2.2 ±0.237	4 ±0.265
3	Friability (%)	0.557 ±0.149	0.642 ± 0.261	0.577 ±0.153	0.275 ±0.055	0.138 ±0.159
4	Disintegration time (sec)	41.33 ±1.527	40.33 ±0.577	40 ±1	2.7(min) ±0.305	3.7 (min) ±0.36
5	Water absorption ratio	102.8 ±3.15	100.01 ±0.66	100.96 ± 0.404	71.6 ±1.382	61.40 ±0.37
6	Uniformity of content (%)	Pass	Pass	Pass	Pass	Pass
7	Percentage release after 10 min ( ± %).For control after 30 min	99.60 ±1.89	99.66 ± 0.35	99.811 ±21.54	98.18 ±0.94	98.06 ±2.82

Figure 1: I.R. spectra of powder blend of drug and Ac-Di- Sol

Figure 2: DSC curve for Sodium Starch Glycolate and powder blend with drug.

Figure 3: DSC curve for Indion 414 and powder blend with drug.

Tizanidine is also used to treat lower back pain, headaches, and trigeminal neuralgia.⁵"Upon review of the

pivotal clinical studies, the FDA recognizes that tizanidine is safe and effective for the treatment of a variety of patients who suffer from the debilitating symptoms of spasticity. This is welcome news for the many patients whose spasticity could not be effectively treated with existing options.⁴

MATERIALS AND METHODS: Tizanidine hydrochloride, sodium starch glycolate, cross carmellose sodium, microcrystalline cellulose, starch, aerosil, menesium stearate, D-mannitol, were supplied by NuLife pharmaceuticals, Pimpri, Pune, Indion 414 was supplied by Ion exchange India Ltd.Mumbai, all the mateials used were of standard analytical grade.

▪ Preparation of Powder Blend of Drug and Excipients: ^{6, 7}

Fast dissolving/ disintegrating tablets of Tizanidine hydrochloride were prepared using direct compression method after incorporating different superdisintegrants such as, Crosscarmellose sodium (Ac-Di-Sol), Sodium starch glycolate and Indion 414 in different concentrations. Formulation for mouth dissolving tablets were given in Table 1.

Evaluation of Mixed Powder Blend of Drug and Excipients: ^{8, 9}

The I.R. Spectrums of drug and excipients were taken to check any possible interaction. The I.R. spectrums were determined by using FTIR, and the results are shown in figure 1.

Differential Scanning Calorimetry was also performed to check the interaction of drug with the polymer used. DSC results are shown in figure 2 and 3.

Powder blend of drug and excipients were evaluated for Angle of Repose, Bulk Density, Tapped Density, Compressibility Index, and Hausner Ratio to determine flow property. Results of all evaluations of powder blend are summarized in Table 2a and 2b.

▪ Evaluation of Tablets prepared by Direct Compression Method:

All prepared tablets were evaluated for various parameters like weight variation, hardness, friability, disintegration time, Water absorption ratio, % drug release, content uniformity, stability study of compressed tablets, etc. Results are summarized in Table 3a and 3b.

RESULT AND DISCUSSION:

All prepared tablets were compatible with respect to drug and polymers. All the prepared tablets containing super disintegrants shows disintegration time within 1 minute. in which tablets containing Indion 414 require comparatively less time to disintegrate. All the tablets containing super disintegrants dissolve within 10 minutes with the release of more than 97 %, and tablets containing Indion 414 release medicament more than 99%, but the control tablets which didn’t contain any super disintegrant disintegrate more than 2 min. and shows 98 % release of drug after 30 min. Thus super disintegrants play significant role to increase release rate of drug and decrease disintegration time. Among them Indion 414 serve as a better super disintegrant.

REFERENCES:

1. David Brown. Drug Delivery Technology. 2005; 1-7.

2. Manthan M.J, Udhav S.B. Review Manufacturing Technology for Mouth Dissolving Tablets. March 2007; 1-7.

3. Adleeb Ahmad. Functional Foods and Nutraceuticals, New Technology Delivers Faster Melting Tablets. March 2004; 1-3.

4. www. Rx List. com.

5. Tsaus J., Damani H, Nalikant C, US Patent No. US5286489, 1994. Pg. No. 1-5.

6. Mishra D.N., et al. Indian Drugs. 2005; 42(10):685-687.

7. Bhagwati S.P., Hiremanth S,N., Sreenivas S.A. Indian. J.Pharm. Edu.Res. 2005; 39(4):194-197.

8. Vijaya K.S.G., Mishra D.N. Indian Drugs. 2006; 43(2): 117-121.

9. Indian Pharmacopoeia, 4^th Edition, Vol.II, Controller of Publication, Govt. of India, New Delhi 1996, Pg.No. 735.

Received on 05.03.2009

Accepted on 10.05.2009

© A&V Publication all right reserved

Research Journal . of Pharmaceutical Dosage Forms and Technology. 1(1): July.-Aug. 2009, 55-58