INTRODUCTION:

For poorly soluble, orally administered drugs, the rate of absorption is often controlled by the rate of dissolution of the drug in the gastro-intestinal tract. Although theoretically the dissolution rate can be, enhanced by increasing the surface area of the drug by micronization, in practice the effect of micronization is often disappointing, especially when the drugs are tableted. The importance of quick tablet disintegration and dissolution to ensure rapid availability of the active ingredient(s) for absorption is well recognized^1-4. A number of agents have been formerly used as tablet disintegrants but are now archaic. Only a few acceptable disintegrants are currently available to pharmaceutical scientists. The plain starches were the most widely used disintegrants but could not be used in low concentrations to effectively break apart the tablet^5-6. Most compendia and industry standards for the disintegration time of a compressed tablet are considerably shorter than they were in the early 1970s. This shorter disintegration time requirement stimulated continuous efforts in the search for new, more efficient disintegrating agents other than the most widely used plain starches.

Traditional tablet disintegrants can be classified as starch (e.g. corn, wheat, potato, rice and pregelatinized starch), macromolecules (e.g.alginic acid, sodium alginate, polacrilin potassium, and guar gum), finely divided solids (e.g. colloidal silicon dioxide and magnesium aluminum silicate), and cellulose (e.g. powdered cellulose, microcrystalline cellulose, carboxymethylcellulose, methylcellulose, and low-substituted hydroxypropylcellulose). Wicking and swelling were found to be the primary mechanisms of action for tablet disintegrants, while other mechanisms, such as deformation recovery, particle repulsion theory, heat of wetting and evolution of a gas etc., may play a role in particular cases of tablet disintegration^7-9.

In present work, the drug is Domperidone which predominantly antagonizes the dopamine D2 receptor without major involvement of other receptors and effectively used in migraine prophylaxis. But Domperidone is poorly water soluble drug and its bioavailability is more likely due to disintegration process¹⁰. KYRON T 314 is derived from cross linked polymer of polycarboxylic acid as per USP/NF and has a K⁺ ionic form. It is a very high purity polymer used in pharmaceutical formulation as a super fast disintegrant as well as dissolution improver in solid dosage form like tablet, Capsule, Pellets etc. The purpose of the current study was to evaluate KYRON T314 as a tablet disintegrant in direct compression formulations in comparison with three other super disintegrants, i.e. croscarmellose sodium, crospovidone, and sodium starch glycolate.

MATERIALS AND METHOD:

KYRON T314 was obtained from Corel Pharma Chem, Ahmedabad; Domperidone was obtained as gift sample from JCPL Pharma Ltd, Jalgaon. All other chemicals were of pharmaceutical grade.

Preparation of Fast Dissolving Tablet:

Domperidone was selected as the model drugs and the tablet compositions used in this study are shown in Table 1. All the components of any given formulation except the lubricant were mixed in a Turbula mixer (Glenmills, Clifton, NJ) at 30 rpm for 5 min. The powder blends were screened through a US 20 mesh screen and the screened powder blends were lubricated with magnesium stearate and talc in a Turbula mixer at 30 rpm for 5 min. The tablets were compressed on 16 stations rotary tabletting machine (Cadmach, Ahmedabad) using 6.8 mm flat punches. Weight of each batch was adjusted to 100 mg.

Evaluation of Domperidone Tablets:

Prepared tablet were evaluated for weight variation,friability,disintegration time,wetting time and drug content. In weight variation test, 20 tablet were selected random and average weight variation was calculated.Then individual tablet were weighed and weight was compared with average weight.

Pfizer hardness tester was used for the determination of hardness of tablets. The tablet was placed in contact between the plungers and handle was pressed. The force of fractured was recorded.

The friability of all the tablets studied was determined using a Roche friabilator.

In the disinteration time study,the tablet was put into 100 ml distilled water at 37 ± 2^oC. Time required for complete dispersion of a tablet was measured with the help of a digital tablet disintegration test apparatus.

In wetting time study, a piece of tissue paper folded twice was placed in a small petridish containing 5 ml of distilled water.A tablet was placed on the paper and time for complete wetting of tablet was measured in seconds.

For the determination of the drug content, a total 10 tablet were weighed and powder equivalent to 10 mg of Domperidone was weighed and dissolved in methanol then filtered through Whatman filter paper. Solution was analysed for Domperidone content by UV-Spectrophotometer at 287 nm using methanol as blank.

In-Vitro Dissolution Test :

The in-Vitro dissolution study was carried out in the USP dissolution test apparatus (Electrolab TDT-08 L Dissolution tester USP ) type 2 (paddle).Nine hundred milliliter of dissolution medium (0.1 N HCl) and temperature was maintained at 37±0.5^oC. The speed of paddle was set at 75 rpm. Sampling was performed at every 1 min-interval. For each sample, 5 ml of dissolution medium was withdrawn and same amount of dissolution medium at 37±0.5^oC was replenished to the dissolution medium. Sample was withdrawn and diluted with 0.1 N HCl and analysed by UV-Spectrophotometer at 287 nm using 0.1 N HCl as blank.

RESULTS AND DISCUSSION:

The data obtained from post-compression parameter such as weight variation, hardness, friability, wetting time, drug content and in vitro disintegration are shown in Table 2. In all formulation, the hardness test indicated good mechanical strength, whereas friability is less than 1% which indicated that tablet had good mechanical resistance.

Drug content was found to be high (>99.20) and uniform in all tablet formulations. It was ranged from 98.92 to 99.85 and uniform in all tablet formulations. An ultraviolet (UV) spectrophotometric method was used for the determination of drug content. Absorption maxima was determined by scanning different concentration of solution of drug Domperidone. Absorption maxima was 287 nm and method obeys Beer's law in concentration range 5 to 50 μg/ml, with good correlation coefficient (0.9997).When a standard drug solution was assayed repeatedly (n=6),relative error (accuracy) and relative standard deviation (precision) were found to be 0.72 and 0.93% respectively.

The tablets were subjected for evaluation of the in-vitro disintegration time and it was observed that the time for formulation varied from 10 to 52 second. It was observed that when KYRON T314 and CCS were used as disintegrant, tablet were disintegrate within short time due to easy and high swelling ability of KYRON T314 and CCS. It is observed that disintegration time of tablet decreased with increased in concentration of CCS, CP, and KYRON T-314. However, the disintegration time increased with increase in the level of SSG in the tablet. It indicates that the increase in level of SSG had a negative effect on disintegration of tablet. At higher levels, formation of viscous gel layer by SSG might have formed a thick barrier to the further penetration of disintegration medium and hindered the disintegration or leakage of tablet content. Thus, tablet disintegration is retarded to some extent with tablets containing SSG when compared with the disintegration time of tablet containing CCS, CP, and KYRON T-314.

Fig 1: Dissolution Profile of Different formulation

Table 1: Composition of Domperidone Fast Dissolving Tablet :

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12
Domperidone	10	10	10	10	10	10	10	10	10	10	10	10
SSG	2.5	5	10	-	-	-	-	-	-	-	-	-
CP	-	-	-	2.5	5	10	-	-	-	-	-	-
CCS	-	-	-	-	-	-	2.5	5	10	-	-	-
KYRON T 314	-	-	-	-	-	-	-	-	-	2.5	5	10
MCC	35	35	35	35	35	35	35	35	35	35	35	35
Mg-Stearate	3	3	3	3	3	3	3	3	3	3	3	3
Talc	3	3	3	3	3	3	3	3	3	3	3	3
Lactose	46.5	44	39	46.5	44	39	46.5	44	39	46.5	44	39
TOTAL (mg)	100	100	100	100	100	100	100	100	100	100	100	100

Table 2: Results of the post compression parameters

Formulation	Hardness Kg/cm²	Friability (%)	Drug Content (mg%)	Disintegration Time(S)	Wetting time(S)	Weight Variation(mg)
F1	3.8	0.62±0.12	99.22	45	52	100.32±2.7
F2	3.5	0.69±0.14	98.92	49	59	100.29±2.1
F3	3.3	0.65±0.11	99.85	52	66	100.10±2.4
F4	3.5	0.62±0.11	99.72	42	55	100.43±2.1
F5	3.6	0.60±0.14	99.35	40	51	99.97±1.4
F6	3.9	0.67±0.13	99.67	37	48	100.55±2.4
F7	3.4	0.63±0.16	99.65	30	53	100.84±2.1
F8	3.6	0.60±0.11	99.78	28	47	100.65±2.4
F9	3.5	0.65±0.14	99.79	24	44	100.64±2.1
F10	3.9	0.67±0.14	99.39	18	39	100.1±2.0
F11	3.5	0.69±0.12	99.89	11	31	100.3±2.1
F12	3.9	0.68±0.17	99.90	10	25	100.21±2.3

Fig 2: Dissolution Profile of Different CP SSG formulation

Fig 3:Dissolution Profile of Different CCS formulation

Fig 4:Dissolution Profile of Different KYRON T 314 formulation

In-Vitro Dissolution Test:

Because the dissolution process of tablet depends on the wetting of tablet, the measurement of wetting time may be used as another confirmative test for evaluation of the fast dissolving tablet. In wetting time study, the wetting time was rapid in KYRON T-314 followed by, CP and CCS. However in case of SSG, as the concentration increased, time taken for wetting also increased. The influence of superdisintegrant on dissolution of domperidone from tablet shown in fig.1, 2, 3, 4. t_50% and t_90%(time for 50% and 90% of release) value decreased with increase in level of CP, CCS, KYRON T 314.However, t_50% and t_90%value increase with increase in level of SSG. Rapid increase in dissolution of Domperidone with increase in KYRON 314 may be attributed to rapid swelling and disintegration of tablet into primary particles. However, tablet prepared with SSG disintegrate by rapid uptake of water followed by rapid and enormous swelling in to primary particle, but more slowly due to the formation of viscous gel layer by SSG. CP and CCS exhibit capillary activity and pronounced hydration, with little tendency to gel formation and disintegrate the tablet rapidly but into larger masses of aggregated particle. Thus difference in size distribution generated and differences in surface area exposed to the dissolution with different super disintegrant rather than speed of disintegration of tablet may be attributed to the the differences in t_50% and t_90% values with the same amount of superdisintegrant in tablet.

CONCLUSION:

Major problem of Domperidone is that it is erratically absorbed from the gastrointestinal tract and its limited water solubility, which may hinder dissolution. Result reveled that it is possible to enhance the dissolution rate and bioavailability by direct compression technique using different superdisintegrants. The overall results indicate that formulation F12, which contain 10% KYRON T 314, was better and that it satisfies all the criteria as a fast dissolving tablet.

ACKNOWLEDGEMENT:

The authors are thankful to JCPL, Jalgaon and MAEER’s Maharashtra Institute of Pharmacy, Pune for providing the required facilities, guidance and support.

REFERENCES:

1) Mukesh Gohel et al. Formulation Design and Optimization of Mouth Dissolve Tablets of Nimesulide Using Vacuum Drying Technique. AAPS PharmSciTech 2004; 5 ,3: Article 36.

2) Simone Schiermeier, Peter Christian Schmidt Fast dispersible ibuprofen tablets. European Journal of Pharmaceutical Sciences 2002; 15: 295–305.

3) Honey Goel et al. A Novel Approach to Optimize and Formulate Fast Disintegrating Tablets for Nausea and Vomiting. AAPS PharmSciTech, 2008; 9, 3: 774-780.

4) Sameer G. Late et al. Effects of disintegration-promoting agent, lubricants and moisture treatment on optimized fast disintegrating tablets. International Journal of Pharmaceutics 2009; 365: 4–11.

5) X. Y. Bi et al. Evaluation of rapidly disintegrating tablets prepared by a direct compression method. Drug Dev. Ind. Pharm. 1999; 25:571–581.

6) Shangraw R et al. A new era of table disintegrants. Pharm. Technol. 1980;4: 49–57.

7) Bi, Y., Sunada et al. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem. Pharm. Bull. 1996; 44: 2121–2127.

8) N.G Raghvendrarao et al. Development and evaluation of carbamazepin fast dissolving tablet prepared with complex by direct compression technique. Asian Journal of Pharmaceutics April-June 2009:97-103.

9) Caramella C et al. The role of swelling in the disintegration process. Int. J. Pharm. Technol. Prod. Manuf. 1984; 2: 1–5.

10) Mandell GL. and. Petri WA. Drugs Affecting Gastrointestinal Function. In Goodman and Gilman`s. The pharmacological basis of therapeutics, Edited by Hardman JG and Limbird LE. McGraw-Hill, New York. 1996; 9th ed: pp. 634-635

Received on 03.06.2010 Modified on 16.06.2010

Research J. Pharm. and Tech.3 (4): Oct.-Dec.2010; Page 1029-1032