INTRODUCTION:

Oral routes of drug administration have wide acceptance up to 50-60% of total dosage forms. Solid dosage forms are popular because of ease of administration, accurate dosage, self-medication, pain avoidance and most importantly the patient compliance. The most popular solid dosage forms are being tablets and capsules; one important drawback of this dosage forms for some patients, is the difficulty to swallow. For these reason, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention. Or dispersible tablets are not only indicated for people who have swallowing difficulties, but also are ideal for active people. Fast dissolving tablets are also called as mouth-dissolving tablets, melt-in mouth tablets, Orodispersible tablets, rapimelts, porous tablets, quick dissolving etc.

Fast dissolving tablets are those when put on tongue disintegrate instantaneously releasing the drug which dissolve or disperses in the saliva. The faster the drug into solution, quicker the absorption and onset of clinical effect¹.

Criteria for Fast dissolving Drug Delivery System²:

· The tablets should not require water to swallow, but it should dissolve or disintegrate in the mouth in matter of seconds.

· Be compatible with taste masking.

· Be portable without fragility concern.

· Have a pleasant mouth feel.

· Leave minimum or no residue in the mouth after oral administration.

· Exhibit low sensitive to environmental condition as temperature and humidity.

· Allow the manufacture of the tablet using conventional processing and packaging equipments at low cost.

Salient Feature of Fast Dissolving Drug Delivery System³:

· 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 paediatric, geriatric and psychiatric patients.

· No need of water to swallow the dosage form, which is highly convenient feature for

· Patients who are travelling 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.

· Pregastric 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.

Benefits of fast dissolving tablets⁴:

· Administered without water, anywhere, any time.

· Suitability for geriatric and pediatric patients, who experience difficulties in swallowing and for the other groups that may experience problems using conventional oral dosage form, due to being mentally ill, the developmentally disable and the patients who are un-cooperative, or are on reduced liquid intake plans or are nauseated.

· Beneficial in cases such as motion sickness, suede 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.

Limitations of Mouth Dissolving Tablets⁵:

§ 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.

Common techniques for manufacturing of MD tablets are⁶:

· Lyophilization

· Moulding

· Direct Compression

· Cotton Candy Process

· Spray Drying

· Sublimation

· Mass Extrusion

· Nanonization

· Fast Dissolving Films

2. MATERIALS AND METHOD:

Scopolamine was obtained as gift sample from Anazeal Reasearch Lab, Mumbai. Crosscarmellose sodium, Sodium Starch Glycolate, Indion 414, Mannitol SD 200, Microcrystalline cellulose, Povidone, Magnesium stearate, Talc and Aspartame was obtained from S.D. Fine Chemicals, Mumbai.

3. Experimental Details^7-10

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 Scopolamine and excipients proposed to incorporate into the formulation. Scopolamine 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 Preparation Tablet by Direct Compression

The fast dissolving tablets prepared by superdisintegrant addition method. The superdisintegrant (Cross Carmellose Sodium, Indion 414 and Sodium Starch glycolate) were used to formulate the tablets. The tablets were formulated employing direct compression method according to the formula given in Table No. 1 using 8 mm biconcave punches. It is the process by which tablets are compressed directly from mixtures of the drug and excipients without preliminary treatment such as granulation.

Scopolamine hydrobromide (0.4 mg), super disintegrants in different ratios (Table no. 1) 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 a lubricant. The granules 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 Fast-disssolving tablets (200 mg)

Ingredients (mg)	F1	F2	F3	F4	F5	F6	F7	F8	F9
Scopolamine Hydrobromide	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4	0.4
MCC (PH-102)	120	120	120	120	120	120	120	120	120
Crosscarmellose sodium	10 (5%)	20 (10%)	30 (15%)	-	-	-	-	-	-
Indion 414	-	-	-	10 (5%)	20 (10%)	30 (15%)	-	-	-
Sodium Starch Glycolate	-	-	-	-	-	-	10(5%)	20(10%)	30(15%)
Povidone	1	1	1	1	1	1	1	1	1
Pearlitol SD200	64.6	54.6	44.6	64.6	54.6	44.6	64.6	54.6	44.6
Aspartame	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s
Talcum powder	2	2	2	2	2	2	2	2	2
Mg. Stearate	2	2	2	2	2	2	2	2	2

4. RESULT:-

4.1 Identification by FT-IR

Fig. No. 1:- IR Spectra of Scopolamine 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 methanol, water Slightly soluble in Acetone and chloroform.	Complies
3.	Identification by FTIR	To match with working standard	Matches with the working standard
4.	Melting range	195⁰C	Complies
5.	Sulphated ash	Not more than 0.1%	Complies
6.	Loss on drying	Not more than 0.5%	Complies
7.	Heavy Metals	20 ppm max	Complies
8.	Assay	98.0-100.5%	Complies

4.3 Preformulation Study

Preformulation testing is an investigation 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.

Table 3: Preformulation study of pure drug Scopolamine

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 methanol, water Slightly soluble in Acetone and chloroform.	Complies
3.	Melting range	195 °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

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

Table no. 4: 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+ Sodium Starch Glycolate	1:10	off -White	off -White	off -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

4.5 Evaluation of Floating tablets

Table No. 5: Evaluation of Mouth dissolving tablets

Batch	F1	F2	F3	F4	F5	F6	F7	F8	F9
TEST	MICROMERETIC PROPERTIES
Angle of repose (θ)	29⁰12’	30⁰56’	32⁰70’	30⁰33’	29⁰81’	32⁰76’	35⁰64’	28⁰91’	31⁰03’
Bulk density (g/ml)	0.55	0.59	0.58	0.53	0.57	0.52	0.54	0.58	0.54
Tapped density (g/ml)	0.73	0.79	0.78	0.70	0.71	0.67	0.69	0.69	0.66
Compressibility Index (%)	23.60	25.22	23.61	20.03	19.42	21.57	20.38	18.93	21.32
Hausener’s ratio	1.32	1.34	1.34	1.32	1.25	1.29	1.28	1.19	1.22
PHYSICAL EVALUATION OF FORMULATED TABLET BATCHES
Thickness (mm)	2.64	2.61	2.63	2.56	2.56	2.58	2.62	2.64	2.61
Hardness (kg/cm²	4.6	4.2	4.0	4.5	4.0	4.0	4.8	4.5	3.0
Friability (%) ±SD	0.26	0.72	1.16	0.14	0.34	0.37	0.57	0.42	1.03
Wetting time (sec)/ ± SD	52	46	43	48	34	29	49	40	37
Drug Content Uniformity (%)	98.8	98.3	98.7	97.3	96.7	98.2	98.1	97.9	98.4
Disintegration time (sec)/± SD	22	12	10	20	10	09	17	10	09
% DRUG RELEASE
30 sec	7.38	17.08	16.15	28.15	24.92	32.31	7.38	9.23	36.92
60 sec	65.6	75.88	59.26	62.62	84.28	86.67	76.69	85.95	86.26
90 sec	75.2	85.49	83.45	68.39	87.06	87.63	78.47	86.90	87.21
2 min	76.0	86.89	84.37	70.98	88.47	89.05	79.79	87.86	88.16
3 min	76.8	88.29	87.13	74.98	92.66	90.01	82.97	92.50	92.81
4 min	79.4	89.25	88.08	79.02	93.72	93.28	87.09	93.49	94.73
5 min	80.4	91.11	89.48	80.32	94.65	94.27	89.41	94.44	95.73
6 min	88.6	92.54	90.88	83.02	96.11	95.72	90.35	95.49	96.74
7 min	89.4	93.50	91.83	87.11	97.57	98.10	92.21	97.41	98.21
8 min	91.4	94.47	92.77	91.25	99.04	99.57	94.55	98.41	99.68

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

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

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

4.6 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. 6: Drug release kinetic study of optimized batch

MODELS		F₅ (Scopolamine)
Korsmeyer- peppas	n	0.986
Zero order	R	0.978
First order	R	0.845
Higuchi model	R	0.996
Best fit model		Higuchi

Fig No. 5: Curve fitting data of the release rate profile of zero order.

Fig No.6: Curve fitting data of the release rate profile of first order.

Fig No.7: Curve fitting data of the release rate profile of Higuchi model

Fig No.8: Curve fitting data of the release rate profile of Korsmeyer-peppas