1. INTRODUCTION:

Mouth dissolving tablet (MDT) is a tablet that disintegrates and dissolves rapidly in the saliva, within a few seconds without the need of drinking water or chewing. A mouth dissolving tablet usually dissolves in the oral cavity within 15 s to 3 min. Most of the MDTs include certain super disintegrants and taste masking agents¹.

The most important ingredients of a mouth dissolving tablets are Super disintegrants. use of disintegrants is the basic approach in development of MDTs. Disintegrants play a major role in the disintegration and dissolution of MDT. It is essential to choose a suitable disintegrant, in an optimum concentration so as to ensure quick disintegration and high dissolution rates. Super disintegrants provide quick disintegration due to combined effect of swelling and water absorption by the formulation. Due to swelling of superdisintegrants, the wetted surface of the carrier increases, which promotes the wettability and dispersibility of the system, thus enhancing the disintegration and dissolution. The optimum concentration of the superdisintegrant can be selected according to critical concentration of disintegrant. Below this concentration, the tablet disintegration time is inversely proportional to the concentration of the superdisintegrant, whereas if concentration of superdisintegrant is above critical concentration, the disintegration time remains almost constant or even increases. Sodium starch glycolate, Ac‐di‐sol (crosscarmellose sodium), Crospovidone, Microcrystalline cellulose, Pregelatinised starch are some of examples of disintegrants¹

Salient Feature of Fast Dissolving Drug Delivery System²:

Ease of Administration to the patient who cannot swallow, such as the elderly, stroke victims, bedridden patients, patient affected by renal failure and patient who refuse to swallow such as pediatric, geriatric and psychiatric patients.

No need of water to swallow the dosage form, which is highly convenient feature for patients who are traveling and do not have immediate access to water.

Rapid dissolution and absorption of the drug, which will produce quick onset of action.

Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases bioavailability of drug is increased.

Pre gastric absorption can result in improved bioavailability and as a result of reduced Dosage; improve clinical performance through a reduction of unwanted effects.

Good mouth feel property helps to change the perception of medication as bitter pill particularly in pediatric patient.

The risk of chocking or suffocation during oral administration of conventional formulation due to physical obstruction is avoided, thus providing improved safety.

New business opportunity like product differentiation, product promotion, patent extensions and life cycle management.

Beneficial in cases such as motion sickness, sudden episodes of allergic attack or coughing, where an ultra rapid onset of action required.

An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs, due to rapid disintegration and dissolution of these tablets.

Stability for longer duration of time, since the drug remains in solid dosage form till it is consumed. So, it combines advantage of solid dosage form in terms of stability and liquid dosage form in terms of bioavailability.

Limitations of Mouth Dissolving Tablets²:

The tablets usually have insufficient mechanical strength. Hence, careful handling is required. The tablets may leave unpleasant taste and/or grittiness in mouth if not formulated properly.

Newer manufacturing technologies used now days for MDT’s³:

Some of the new advanced technologies which are commonly being used in last few decades are summarized as:-

a) Freeze drying/Lyophilization

b) Molding

c) Direct Compression

d) Cotton Candy Process

e) Spray Drying

f) Sublimation

g) Mass Extrusion

h) Nanonization

i) Fast Dissolving Films

2. MATERIALS AND METHOD:

Astemizole was obtained as gift sample from Anazeal Reasearch Lab, Mumbai. Crosscarmellose sodium, Crosspovidone Indion 414; Mannitol SD 200 was obtained from Mahalakshmi chemicals, Hyderabad. Microcrystalline cellulose, Povidone, Magnesium stearate, Talc and Aspartame was obtained from Samar Chemicals, Nagpur.

3. EXPERIMENTAL DETAILS^4-10

3.1 Characterization of Pure Drug

Pure Drug has been characterize by various parameters like Solubility, Identification by FT-IR, Melting range, Sulphated ash, Loss on drying, Heavy Metals and Assay.

3.2 Preformulation Study

Preformulation testing was done to investigate of physical and chemical Properties of a drug substance alone and when combined with excipients. It is the first step in the rational development of dosage forms.

3.3 Compatibility Study

To analyze the compatibility between Astemizole and excipients proposed to incorporate into the formulation. Astemizole is mixed with excipients in different ratio. These mixtures were kept in a 6ml glass white colour vials and packed properly. These vials are exposed to Room temperature, 30°c / 65% relative humidity and 40˚c / 75%RH.16 gm of blend is prepared which is filled in 3 vials

3.4 Method of Preapration of Mouth Dissolving Tablet by Direct Compression

Drug (10 mg), super disintegrants in different ratios and excipients were blended using mortar and pestle. The drug and the disintegrants were sieved through mesh # 120 before blending. The mixture was evaluated for angle of repose, bulk density and compressibility. The mixture was mixed with 1% magnesium stearate as lubricant and mint as flavoring agent. The powder blends were then compressed by using Fluidpack multistation rotary tablet machine using 8 mm punch. The hardness was adjusted to 2-5 kg/cm2.

Table No. 1: Formulation of Mouth Dissolving Tablet

Ingredients(mg)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Astemizole	10	10	10	10	10	10	10	10	10
MCC (PH-102)	39	39	39	39	39	39	39	39	39
Crosscarmellose sodium	9	13.5	18	-	-	-	-	-	-
Crosspovidone	-	-	-	9	13.5	18	-	-	-
Indion 414	-	-	-	-	-	-	9	13.5	18
Povidone	1	1	1	1	1	1	1	1	1
Pearlitol SD200	89	84.5	80	89	84.5	80	89	84.5	80
Aspartame	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s
Talcum powder	1%	1%	1%	1%	1%	1%	1%	1%	1%
Mg. Stearate	1%	1%	1%	1%	1%	1%	1%	1%	1%

4. RESULT:

4.1 Identification by FT-IR

Fig. No. 1:- IR Spectra of Astemizole Powder

4.2 Characterization of Pure Drug

Table No. 2: Characterization of Pure Drug

Sr. No	Characterization	Specification	Result
1	Description	White or almost white, crystalline powder, odourless or almost odourless.	A almost white powder
2	Solubility	Freely soluble in ethanol (95%), in chloroform and in DMSO; partly soluble in water	Complies
3.	Melting range	172.9 °C	Complies
4.	Identification by FT-IR	To match with working standard	Matches with the working standard
5.	Loss on drying	Not more than 0.5%	Complies
6.	Assay	98.0-100.5%	Complies

4.3 Compatibility Study at Room temperature, 30°c / 65% relative humidity and 40˚c / 75%RH

Table no. 3: Compatibility Study

Sr. No	Drug + Excipients	Proportion	Initial Observation of color	Final observation		Conclusion
Sr. No	Drug + Excipients	Proportion	Initial Observation of color	2^nd week	4^th week	Conclusion
1.	Drug	NA	White	White	White	Compatible
2.	Drug+ MCC (PH-102)	1:10	White	White	White	Compatible
3.	Drug+Crosscarmellose sodium	1:10	White	White	White	Compatible
4.	Drug+ Crosspovidone	1:10	Creamy -White	Creamy - White	Creamy - White	Compatible
5.	Drug + Indion 414	1:10	White	White	White	Compatible
6.	Drug + Povidone	1:10	White	White	White	Compatible
7.	Drug + Pearlitol SD200	1:10	White	White	White	Compatible

4.4 Evaluation of Floating tablets⁴

Table No. 4: Evaluation of Mouth dissolving tablets

Batch	F1	F2	F3	F4
TEST	MICROMERETIC PROPERTIES
Angle of repose(θ)	33.13⁰± 0.003	1.16 ± 0.802	33.25⁰± 0.045	31.21⁰± 0.675
Bulk density (g/ml)	0.47 ± 0.007	0.44 ± 0.017	0.56 ± 0.024	0.48 ± 0.003
Tapped density (g/ml)	0.54± 0.003	0.50± 0.017	0.66± 0.038	0.54 ± 0.003
Compressibility Index (%)	14.23± 1.601	12.62± 1.032	15.15± 1.926	12.40± 0.954
Hausener’s ratio	1.16 ± 0.802	1.14 ± 0.010	1.16 ± 0.802	1.14 ± 0.010
PHYSICAL EVALUATION OF FORMULATED TABLET BATCHES
Thickness (mm)	2.61 ±0.00	2.64 ±0.01	2.63 ±0.01	2.62 ±0.01
Hardness (kg/cm²⁾±SD	3.6 ±0.17	3.2 ±0.19	2.9 ±0.07	3.4 ±0.10
Friability (%) ±SD	0.21 ±0.11	0.73 ±0.06	1.16 ±0.21	0.53 ±0.00
Weight Variation (mg) ±SD	19 ±0.51	14 ±1.21	16 ±0.50	15 ±0.86
Drug Content Uniformity (%)	87.53 ±0.20	87.80 ±0.10	88.16 ±0.01	87.48 ±0.22
Disintgration time (sec)/± SD	25 ±0.86	21 ±0.54	22 ±0.19	27 ±1.57
Dissolution (%w/v)/± SD	67.71±5.83	81.32±1.02	69.0 ±5.38	89.43±1.84
% DRUG RELEASE
30 sec	9.44	14.73	11.08	13.72
60 sec	20.41	29.76	21.87	27.75
90 sec	31.71	48.40	33.40	41.55
2 min	43.18	61.49	44.98	57.26
3 min	53.33	77.80	56.80	73.12
4 min	67.71	81.32	69.0	89.43

Batch	F5	F6	F7	F8	F9
TEST	MICROMERETIC PROPERTIES
Angle of repose(θ)	38.36⁰± 1.852	33.74⁰± 0.219	32.05⁰± 0.378	31.03⁰± 0.738	32.82⁰± 0.106
Bulk density (g/ml)	0.45 ± 0.014	0.47 ± 0.007	0.48 ± 0.003	0.51 ± 0.007	0.53 ± 0.014
Tapped density (g/ml)	0.48 ± 0.024	0.50 ± 0.017	0.56 ± 0.003	0.54 ± 0.003	0.60 ± 0.017
Compressibility Index (%)	5.20± 1.590	5.25± 1.573	6.36± 1.180	4.42± 1.866	11.66± 0.692
Hausener’s ratio	1.06 ± 0.017	1.06 ± 0.017	1.14 ± 0.010	1.04 ± 0.024	1.13 ± 0.007
PHYSICAL EVALUATION OF FORMULATED TABLET BATCHES
Thickness (mm)	2.64 ±0.01	2.61 ±0.00	2.51 ±0.02	2.52 ±0.02	2.54 ±0.01
Hardness (kg/cm²⁾±SD	3.1 ±0.00	3.4 ±0.10	3.2 ±0.19	2.9 ±0.07	2.5 ±0.21
Friability (%) ±SD	0.41 ±0.04	1.07 ±0.18	0.12 ±0.14	0.32 ±0.07	0.33 ±0.07
Weight Variation (mg) ±SD	18 ±0.19	19 ±0.55	16 ±0.50	12 ±1.92	28 ±3.73
Drug Content Uniformity (%)	87.80 ±0.10	78.40 ±3.43	87.96 ±0.05	95.11 ±0.93	92.76 ±1.64
Disintgration time (sec)/± SD	24 ±0.51	25 ±0.86	23 ±0.15	17 ±1.96	19 ±1.25
Dissolution (%w/v)/± SD	85.53±0.46	87.93±1.31	89.98±2.03	95.48±3.98	91.68±2.63
% DRUG RELEASE
30 sec	14.96	13.5	14.58	14.73	14.17
60 sec	29.95	27.47	29.55	29.33	28.68
90 sec	45.7	41.73	45.0	45.08	43.13
2 min	61.71	36.96	61.61	61.28	59.17
3 min	78.1	72.6	77.36	78.16	75.15
4 min	85.3	87.93	89.98	95.48	91.68

Fig. No. 2: Comparative study of % Drug release (Batch F1, F2 and F3)

Fig No. 3: Comparative study of % Drug release (Batch F4, F5 and F6)

Fig No. 4: Comparative study of % Drug release (Batch F7, F8 and F9)

4.5 Mechanism of Release from Matrix tablets:

From the data obtained after applying all suitable mathematical models we can conclude that the optimized formulations selected are proposed to explain the mechanism of release of drug from formulation

Table no. 5: Drug release kinetic study of optimized batch

MODELS		F₈ (Astemizole)
Korsmeyer- peppas	n	0.987
Zero order	R	0.976
First order	R	0.846
Higuchi model	R	0.996
Best fit model		Higuchi