ABSTRACT

This study investigated to compare the disintegration efficiency for the 5 classes of superdisintegrants represented by Cros-carmellose Sodium (CCS), Cros-povidone (CP), Polacrilin K (PK), Sodium Starch Glycolate (SSG), and L-Hydroxy Propyl Cellulose (L-HPC). Tablets were prepared by direct compression method. Effect of 5 superdisintegrants on disintegration time, dissolution parameters, and friability has been studied. Among all the superdisintegrants, a PK containing tablets has shown faster disintegration followed by SSG. Tablets containing L-HPC disintegrated after PK and SSG containing tablets.

Where as disintegration time and dissolution parameters increased with increase in the level of Cros-carmellose in tablets. However the disintegration time value did not reflect in dissolution parameter values of cros-povidone tablets and release was dependent on aggregate size in dissolution medium.

KEYWORDS: Orodispersible Tablets, Olanzapine, Superdisintegrants.

INTRODUCTION

Despite increasing interest in controlled-release drug delivery systems, the most common tablets are those intended to be swallowed whole and to disintegrate and release their medicaments rapidly in the gastrointestinal tract (GIT). The proper choice of disintegrants and its consistency of performance are of critical importance to the formulation development of such tablets. In recent years, increasing attention has been paid to formulating orally disintegrating tablets that are intended to dissolve and/or disintegrate rapidly in mouth. Now a days role and use of superdisintegrants increases because of its high efficiency.^1-4

Significance: -

· Unit dosage form.

· Clinical benefit in patient with dysphasia (Swallowing difficulties)

· No risk of obstruction of dosage form

· Easy to administered for instructionalized patients (specially for psychiatric patients)

· Increased compliance & bioavailability

· Pre-gastric absorption avoids metabolism

Challenges: -

· Rapid disintegration of tablet

· Avoid increase in tablet size

· Sufficient mechanical strength

· Minimum or no residue in mouth

· Protection from moisture

Olanzapine is 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2, 3-b] [1, 5] benzodiazepine, an antipsychotic drug belongs to thienobenzodiazepine derivatives which are practically insoluble in water.

Table 1: Composition of Orodispersible Tablets

Ingradients (mg)	O1	O2	O3	O4	O5	O6	O7	O8	O9	O10
Drug	10	10	10	10	10	10	10	10	10	10
Polacrillin Potassium	7.5	-	-	-	-	12.5	-	-	-	-
Sodium Starch Glycolate	-	7.5	-	-	-	-	12.5	-	-	-
Crospovidone	-	-	7.5	-	-	-	-	12.5	-	-
Croscarmellose Na	-	-	-	7.5	-	-	-	-	12.5	-
L-HPC	-	-	-	-	7.5	-	-	-	-	12.5
MCC	45	45	45	45	45	45	45	45	45	45
Lactose	86.5	86.5	86.5	86.5	86.5	81.5	81.5	81.5	81.5	81.5
Mg. Stearate	1	1	1	1	1	1	1	1	1	1

* All formulations were contains 0.05% of Butylated Hydroxy Anisole as an antioxidant.

Table 2: Physical evaluation parameters of formulations O1-O10.

Formulations	Hardness (kg/cm²) Mean ± S.D.	Thickness (mm) Mean ± S.D.	Friability (%) Mean ± S.D.	Disintegration Time (Sec) Mean ± S.D.
O₁	5.2 ± 0.29	1.7 ± 0.05	0.210±0.025	10.0±2.0
O₂	4.8 ± 0.52	1.8 ± 0.00	0.340±0.030	15.0±2.0
O₃	5.4 ± 0.29	1.7 ± 0.03	0.470±0.035	22.0±3.0
O₄	4.9 ± 0.52	1.7 ± 0.02	0.310±0.015	18.0±2.0
O₅	4.9 ± 0.59	1.8 ±0.02	0.275±0.025	13.0±3.0
O₆	5.3 ± 0.76	1.8 ±0.00	0.195±0.035	8.0±2.0
O₇	5.3 ± 0.72	1.8 ± 0.01	0.310±0.027	13.0±2.0
O₈	5.3 ± 0.53	1.7 ± 0.03	0.435±0.030	21.0±3.0
O₉	5.2 ± 0.53	1.8 ± 0.00	0.265±0.020	15.0±2.0
O₁₀	5.1 ± 0.28	1.8 ± 0.00	0.223±0.015	10.0±3.0

The changes in physiological functions associated with aging including difficulty in swallowing, administration of intact tablet may lead to poor patient compliance and ineffective therapy. To overcome this, dispersible tablets and fast-disintegrating tablets have been developed. Most commonly used methods to prepare these tablets are; freeze-drying / Lyophilization tablet molding and direct-compression methods^5-8. Main advantage of direct-compression is low manufacturing cost and high mechanical integrity of the tablets. Therefore, direct-compression appears to be a better option for manufacturing of tablets. The fast disintegrating tablets by direct-compression method, in general, are based on the action established by superdisintegrants such as Cros-Carmellose Sodium (CCS) Cros-Povidone (CP), Sodium Starch Glycolate (SSG), L-Hydroxy Propyl Cellulose (L-HPC) and Poliacrlin Potassium. The effect of functionality differences of the superdisintegrants on tablets of disintegration has been studied. The objective of the present work was to develop fast dispersible olanzapine tablets and to study the effect of functionality differences of superdisintegrants on the tablet properties and to provide information on the storage conditions of these tablets.^9-16

Fig 1: Release profile of Olanzapine (O1-O5)

M ATERIALS AND METHODS:

Materials:

Olanzapine was obtained as a gift sample from Aventis Pharmaceuticals (Goa), Polacrilin Potassium from Thermax (Pune), Sodium Starch Glycolate (SSG), Cros-Povidone (CP), Cros-Carmellose Sodium (CCS) were generously gifted by Cipla (Mumbai), L-Hydroxy Propyl Cellulose (L-HPC), Microcrystalline Cellulose (MCC) from Wallace Pharmaceutical (Goa), Magnesium Stearate and Lactose from Loba Chemie. Other reagents and organic solvents used were of analytical grade. Buffer and its dilutions were prepared with double-distilled water.

Methods:

Preparation of Olanzapine Orodispersible Tablets:

The tablets were prepared as follow according to the proportion given in the table 1 The raw materials were passed through a no. 120 sieve. All materials mixed in polybag for 20 min and then mixture was lubricated by magnesium stearate before compression. The tablets were compressed using six station rotary tablet compression machine (JM-6, JMC) equipped with 8 mm punch. The tablet weight was adjusted to 150 mg.

Fig 2: Release profile of Olanzapine (O6-O10)

Evaluation of Tablet Properties:¹⁷^-19

Thickness and Crushing strength:

The thickness of the tablet was measured using Vernier caliper and the crushing strength of the tablets was measured using a Monsanto hardness tester.

Friability test:

The friability of a sample of 10 tablets was measured using a Roche Friabilator (Jashbin). Ten preweighed tablets were rotated at 25 rpm for 4 minutes. The tablets were then reweighed after removal of fines (using no. 60 mesh screen), and the percentage of weight loss was calculated.

Disintegration test:

The disintegration time was measured and standard deviation calculated for each, using a disintegration apparatus (META LAB) using 900 ml in pH 1.2 without disk at 37⁰C.

Dissolution Studies:

Dissolution experiments were performed in triplicate with USP XXVII dissolution test apparatus,(Electrolab) in pH 1.2 a simulated gastric fluid (SGF) at 37±0.5⁰C using the paddle method at a rotation speed of 50 rpm. At appropriate time intervals, 10 ml of the mixture was withdrawn and filtered. The removed samples were analyzed at 260 nm by UV-Vis spectrophotometer (UV 530 JASCO).

RESULTS AND DISCUSSION:

The crushing strength of the tablets was adjusted to 5 kilopond (kp) and tablets diameter was 8 mm and the thickness were ~1.8mm. The evaluation parameters of all formulations are shown in table 2.

In the present study, all the tablets disintegrated in ≤ 20 sec fulfilling the official requirements (3 min) for dispersible tablets. It is observed that tablets containing Polacrilin potassium superdisintegrants disintegrates faster than other superdisintegrants containing tablets. Comparatively, disintegration times of tablets containing PK<SSG<L-HPC<CCS<CP. Tablets containing CP, increasing level of CP had no effect on disintegration times of the tablets.

The influence of superdisintegrants on the dissolution of Olanzapine from the tablets is shown in Fig: 1 and 2. The T^90% values decreased with increase in the level of PK, CCS and L-HPC. These results indicated that dissolution parameter values of PK, CCS and L-HPC containing tablets are consistent. The rapid increase in dissolution of Olanzapine with PK, CCS and L-HPC may be attributed to rapid swelling and disintegration of tablets into primary particles.

CONCLUSION:

In the present study, 5 superdisintegrants representing each of the 5 main classes are differed in their ability to disintegrate model tablets into primary particles when used at the same %w/w concentration. Such a difference can potentially affect drug dissolution.

It is concluded that, although functionality differences existed between the superdisintegrants, the orodispersible Olanzapine tablets could be prepared by using any of the superdisintegrants used. The dissolution parameters were consistent with disintegration times of PK and CCS. However T_90%increases with increase in level of SSG because it might have formed a thick barrier for further dissolution. T_90%did not change with increase in level of CP.

ACKNOWLEDGEMENT:

The authors are grateful to Aventis Pharmaceuticals (Goa), Wallace Pharmaceutical (Goa) and Cipla (Mumbai) for providing gift samples.

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Received on 07.08.2009

Accepted on 10.10.2009

Research Journal of Pharmaceutical Dosage Forms and Technology. 1(3): Nov. – Dec. 2009, 233-235