INTRODUCTION:

Dealing with such a classical item as solid dosage form, it could be argued that much work has been done in the superdisintegrant field. This is probably true, since most of the papers on the selection of superdisintegrant on specific drugs are reported. Na Zhao and Larry L. Augsburger reported that Ac-Di-Sol was found to disintegrate tablets rapidly into apparently primary particles compared to Primojel and Polyplasdone XL 10.¹ Bhattu S.K., et al. reported that 6% Crospovidone was selected for Fenoverine tablets.² Piera Di Martino et al. reported was better than Kollidon CL and Vivasol.³ Mulla J.A., et al. stated that Ac-Di-Sol was found to be better suited for the formulation of Promethazine compared to other superdisintegrants used in study.⁴

But on comparison these papers show varying results. Thus, the formulator has a difficulty in selecting these superdisintegrants on the drug of interest. Hence, work was done with the aim so that the choice of superdisintegrant would be easy.

MATERIALS AND METHODS:

Materials:

Diclofenac Free Acid (Amoli Organics), Famotidine (Zydus Healthcare), Tramadol HCl (Spic Ltd.), Avicel PH 102 (FMC Biopolymer), Pearlitol SD 200 (Roquette), Aspartame (Vita Sweet Co. Ltd.), Colloidal silicon dioxide (Cabot Sanmar Ltd), Magnesium stearate (Amishi Drug and Chemicals), Sodium Starch Glycolate [SSG] (Shital Chemicals), Crospovidone [CRP] (BASF), Croscarmellose sodium [CCS] (Signet), and Methacrylic copolymer with divinyl benzene i.e. Polyflash® P-544D [Dosh] (Doshion).

Methods:

Different compositions were prepared as shown in (Table No.1) using different superdisintegrants. All the raw materials were weighed and then sifted through sieve no 40 (except magnesium stearate and colloidal silicon dioxide, which were sifted through sieve no 60). All these ingredients except magnesium stearate were mixed in a double cone blender (Rimek Kalweka HD – 410) for 10 min at 10 rpm. Sifted magnesium stearate was then added to the blend and mixed in the double cone blender for another 2 minutes. The blend was compressed on a 16 station compression machine (CADMACK CMD 4-16/MT) using 9.5mm circular flat bevelled edge punches.

Superdisintegrant concentration	2%	4%	6%	2%	4%	6%	2%	4%	6%
API	Diclofenac free acid			Famotidine			Tramadol HCl
API wt.	46.5	46.5	46.5	40	40	40	50	50	50
Avicel PH 102	100	100	100	100	100	100	100	100	100
Pearlitol SD 200	131.5	125.5	119.5	138	132	126	128	122	116
Aspartame	10	10	10	10	10	10	10	10	10
Doshion	6	12	18	6	12	18	6	12	18
Colloidal silicon dioxide	3	3	3	3	3	3	3	3	3
Mg. stearate	3	3	3	3	3	3	3	3	3
Talc	0	0	0	6	6	6	0	0	0
TOTAL (mg)	300	300	300	306	306	306	300	300	300

Evaluation:

The tablets were evaluated for below given parameters.

1. Uniformity of weight: The weight of 20 from tablets was analyzed for sample mean and standard deviation.

2. Friability: It was calculated from the weight loss of tablets tumbled at 100 revolutions in Electrolab Friabilator (USP) model: EF – 1W.

3. Disintegration Time: It was performed at 24 - 26ºC in water using ELECTROLAB EL – 2L without disks.

Fig. 1: Effect of drug solubility on D.T. of 2% superdisintegrants

Experimental Design:

Formulations containing superdisintegrants (Sodium Starch Glycolate, Crospovidone, Croscarmellose sodium, and Methacrylic copolymer with divinyl benzene i.e. Polyflash® P-544D) in their concentration varying from 2, 4 and 6% were formulated. This experiment aimed at determining the effect of superdisintegrant addition on separate formulations with 3 model drugs based on different BCS classes. For this purpose three model drugs (a representative of the respective classes) such as Diclofenac free acid (Class

II), Famotidine (Class IV), Tramadol HCl (Class I) were studied for superdisintegrant effect on disintegration time.(Table 1)

Fig. 2: Effect of drug solubility on D.T. of 4% superdisintegrants

RESULTS AND DISCUSSION:

At 2, 4, 6% concentration of superdisintegrant, there was a trend that the D.T. of Diclofenac free acid was low but not as low as Famotidine. But Tramadol showed an exuberant D.T.

The effect of disintegrant in soluble matrices is lower than that in insoluble matrices. Tablets containing high concentrations of water soluble drug drugs normally tend to erode, rather than disintegrate, which may result in slow disintegration.

Even though Tramadol dissolves partially upon liquid penetration, thus increasing the viscosity of the penetrating liquid, disintegrants will counter act this effect by promoting wicking and opening up the structure.

Fig. 3: Effect of drug solubility on D.T. of 6% superdisintegrants

It is seen that Diclofenac free acid being insoluble, shows very less disintegration time. Tramadol being soluble shows high disintegration time. Famotidine categorized in the middle too shows both properties. Tramadol, though it is highly soluble, the entire system tries to first take up the water, trying to dissolve rather than disintegrate. Diclofenac free acid however, tries to disintegrate as soon as possible. Famotidine is sparingly soluble; hence it shows both these properties. (Fig. 1-3)

CONCLUSION:

It was seen that Diclofenac free acid (II) being insoluble, shows very less disintegration time. Tramadol (I) being soluble shows high disintegration time. Famotidine (IV) categorized in the middle too shows both properties. Diclofenac free acid however, tries to disintegrate as soon as possible. Famotidine is sparingly soluble; hence it showed both these properties. Thus, it was found that the relationship between disintegration time is dependant on the type of system and in particular the solubility characteristic of the entire system. It was observed that for direct compression, irrespective of the drug class, CRP and Doshion can be used

ACKNOWLEDGEMENT:

The authors are thankful to Piramal Healthcare Limited, Mumbai and MAEER’s Maharashtra Institute of Pharmacy, Pune for providing the required facilities, guidance and support.

REFERENCES:

1. Zhao Na and Augsburger L.L. Functionality Comparison of 3 Classes of Superdisintegrants in Promoting Aspirin Tablet Disintegration and Dissolution. AAPS PharmSciTech, 2005; 6, 4: Article 79.

2. Bhattu S.K., Repka M.A., Majumdar S. and Madhusudan R.Y. Formulation and evaluation of rapidly disintegrating fenoverine tablets: Effect of superdisintegrants, Drug Development and Industrial Pharmacy, 2007; 33, 11: 1225-1232.

3. Di Martino P., Martelli S. and Wehrle P Evaluation of different fast melting disintegrants by means of a central composite design, Drug development and Industrial Pharmacy, 2005; 1: 109-121.

4. Mulla, J.A. and Fatima S. Fast Dissolving Tablets of Promethazine: A Novel Oral Formulation for the treatment of Fractionated Radiotherapy Induced Nausea and Emesis, Indian Drugs, 2008; 45, 4: 314 – 317.

Received on . .2008 Modified on . .2008

Research J. Pharm. and Tech.2 (2): April.-June.2009; Page 335-337