INTRODUCTION:

Drug delivery systems are a magic tool for expanding markets/indications, extending product life cycles and generating opportunities. DDS make a significant contribution to global pharmaceutical sales through market segmentation, and are moving rapidly. Fast disintegrating drug delivery (FDDTs,) can be achieved by various conventional methods like direct compression, wet granulation, moulding, spray drying, freeze drying, sublimation.

In order to allow fast disintegrating tablets to dissolve in the mouth, they are made of either very porous and soft molded matrices or compressed into tablets with very low compression force.^1,2,3 The oral fast‐disintegrating tablets is also known as fast dissolve, rapid dissolve, rapid melt and quick disintegrating tablets. However, the function and concept of all these dosage forms are similar. By definition, a solid dosage form that dissolves or disintegrates quickly in the oral cavity, resulting in solution or suspension without the need for the ministration of water, is known as an oral fast‐ dispersing dosage form. According to European Pharmacopoeia, the ODT should disperse/disintegrate in less than three minutes.⁴ Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly, and is also seen in swallowing conventional tablets and capsules.⁵

Ideal properties of FDT:

· Require no water for oral administration, yet dissolve /disperse/disintegrate in mouth in a matter of seconds.

· Have a pleasing mouth feel.

· Have an acceptable taste masking property.

· Be harder and less friable

· Leave minimal or no residue in mouth after administration. Exhibit low sensitivity to environmental conditions (temperature and humidity).

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

Advantages of fast disintigrating tablets^6,7,8:

· Fast dissolving technology offers: Improved compliance/added convenient new business opportunities product differentiation, line extensionand life cycle management, exclusivity of product promotion, and patent‐life extension.

· No water needed

· No chewing needed

· Better taste

· Improved stability

· Suitable for controlled/sustained release actives

· Allows high drug loading.

· Ability to provide advantages of liquid medication in the form of solid preparation.

· Adaptable and ameanable to existing processing and packaging machinery

· Cost‐ effective

· rapid drug therapy intervention

· Best for patent with oesophageal problems and have

· difficulties of deglutition tablets.

· High drug loading is possible.

· Have acceptable taste and pleasant mouth feeling.

· Leave minimum residue.

Limitations to mouth dissolving tablets⁹

1. Drugs with relatively larger doses are difficult to formulate into MDT e.g. antibiotics like ciprofloxacin with adult dose tablet containing about 500 mg of the drug.

2. Patients who concurrently take anticholinergic medications may not be the best candidates for MDT. Similarly patients with Sjögren's syndrome or dryness of the mouth due to decreased saliva production may not be good candidates for these tablet formulations.

Need to formulate mouth dissolving tablets¹⁰:

The need for non‐invasive drug delivery systems continues due to patient’s poor acceptance and compliance with existing delivery regimes, limited market size for drug companies and drug uses coupled with high cost of disease management. MDT is one such dosage form which is useful for

· Geriatric patients mainly suffering from conditions like hand tremors and dysphasia.

· Pediatric patients who are unable to swallow easily because their central nervous system and internal muscles are not developed completely.

· Traveling patients suffering from motion sickness and diarrhea that do not have easy access to water.

· Patients with persistent nausea for a long period of time are unable to swallow. Especially cancer patients after taking their chemotherapy are too nauseous to swallow the H2 blockers, which are prescribed in order to avoid gastric ulceration.

· Mentally challenged patients, bedridden patients and psychiatric patients.

AIM AND OBJECTIVE:

Aim:

The aim of the present study is to formulate Rosuvastatin Calcium Fast Dissolving tablets by employing super disintegrate.

Objectives:

Oral administration is the most popular route compared to other dosage forms due to ease of ingestion, pain avoidance, versatility and most importantly patient compliance but one important drawback of solid dosage form is the difficulty in swallowing (dysphasia) or chewing in patients particularly pediatric and geriatric patients.

The patient acceptability and compliance are important in design of the novel drug delivery system, one such drug delivery system is Fast Dissolving tablets (FDTs) which has gained acceptance and popularity in the recent times.

The prime factor for the commercial success of Fast Dissolving tablets is, because of its significant impact on patient compliance of all age groups. These dosage forms are designed in such a way that they disintegrate or dissolve in patients fast upon contact with saliva, within seconds without aid of water leading to faster onset of action.

The main objective of this study is to enhance the solubility of Rosuvastatin Calcium using super disintegrates.

MATERIALS AND METHODS:

Rosuvastatin Calcium Procured From (Cadila Healthcare Ltd, India. Provided by SURA LABS, Dilsukhnagar, Hyderabad. Banana Powder purchased from Yarrow Chem. Products. Primojel purchased from S.D. Fine chem., Mumbai. Sodium starch glycolate purchased from Arihant Trading Co., Mumbai. Aspartam purchased from Merck Specialities Pvt Ltd, Mumbai, India. Microcrystalline cellulose purchased from Arihant Trading Co., Mumbai. Talc and Magnesium stearate purchased from Molychem, Mumbai, India.

METHODOLOGY:

Formulation development:

Table1: Formulation table showing various compositions

Ingredients (mg)	Formulation Codes
Ingredients (mg)	R1	R2	R3	R4	R5	R6	R7	R8	R9	R10	R11	R12
Rosuvastatin Calcium	10	10	10	10	10	10	10	10	10	10	10	10
Banana Powder	16	32	48	64	-	-	-	-	-	-	-	-
Primojel	-	-	-	-	16	32	48	64	-	-	-	-
Sodium starch glycolate	-	-	-	-	-	-	-	-	16	32	48	64
Aspartam	10	10	10	10	10	10	10	10	10	10	10	10
Microcrystalline cellulose	107	91	75	59	107	91	75	59	107	91	75	59
Talc	4	4	4	4	4	4	4	4	4	4	4	4
Magnesium stearate	3	3	3	3	3	3	3	3	3	3	3	3
Total Weight	150	150	150	150	150	150	150	150	150	150	150	150

Table 3: Evaluation of pre-compression parameters of powder blend

Formulation code	Angle of repose	Bulk density(gm/mL)	Tapped density (gm/mL)	Carr’s index (%)	Hausner’s ratio
R1	24.30	0.384	0.454	15.37	1.181
R2	27.69	0.324	0.469	28.91	1.449
R3	27.34	0.323	0.469	29.13	1.452
R4	26.04	0.354	0.503	29.62	1.421
R5	27.34	0.351	0.491	28.71	1.403
R6	27.69	0.346	0.485	28.65	1.401
R7	27.69	0.350	0.485	27.83	1.387
R8	27.66	0.338	0.494	28.57	1.463
R9	28.34	0.335	0.470	28.72	1.404
R10	27.69	0.353	0.502	29.68	1.422
R11	26.34	0.336	0.502	28.09	1.494
R12	26.01	0.399	0.559	28.62	1.401

· For each formulation blend of drug and excipients were prepared and evaluated for various pre compression parameters described earlier in methodology chapter.

· The bulk density of all formulations was found in the range of 0.323- 0.399 and tapped density was in the range of 0.454- 0.559.

· The Carr’s index and Hausner’s ratio was calculated from tapped density and bulk density.

Evaluations of post compression parameters of Rosuvastatin calcium ODTS:

Table4: Evaluation of post compression parameters of Rosuvastatin Calcium Fast dissolving tablets

Formulation codes	Average weight (mg)	Hardness (kg/cm²)	Friability (%loss)	Thickness (mm)	Drug content (%)	*In vitro* disintegration Time (sec)
R1	148.35	5.3	0.36	3.19	96.85	18
R2	150.04	4.6	0.59	3.27	99.36	26
R3	149.68	4.1	0.64	3.60	97.54	31
R4	143.52	4.9	0.47	3.12	98.10	13
R5	150.00	4.0	0.75	3.88	99.12	28
R6	147.12	4.5	0.36	3.93	97.85	30
R7	146.89	5.1	0.50	3.45	98.64	20
R8	148.93	5.5	0.49	3.20	99.17	18
R9	146.57	4.9	0.81	3.74	96.39	25
R10	147.50	4.7	0.67	3.15	98.75	20
R11	149.21	5.0	0.59	3.82	95.83	21
R12	149.11	5.3	0.38	3.91	98.45	17

IN VITRO DRUG RELEASE STUDIES OF ROSUVASTATIN CALCIUM:

Table5: Dissolution data of Rosuvastatin Calcium

Time (min)	R1	R2	R3	R4	R5	R6	R7	R8	R9	R10	R11	R12
0	0	0	0	0	0	0	0	0	0	0	0	0
5	12.86	18.95	20.10	31.57	19.71	16.39	20.86	26.93	23.95	31.93	26.34	35.46
10	26.51	26.15	32.95	38.15	26.54	27.14	39.75	33.51	38.12	45.21	50.21	48.12
15	38.75	41.12	46.32	52.96	40.39	38.86	48.90	42.65	47.78	59.75	59.14	69.60
20	56.32	60.92	58.71	78.57	56.90	59.17	69.61	69.40	59.15	68.36	64.50	81.15
25	62.18	67.34	79.46	90.14	64.15	78.25	77.21	86.19	65.39	80.59	82.25	86.28
30	72.57	81.56	91.86	99.31	70.21	81.93	87.33	92.12	81.42	87.42	90.19	97.32

Fig2: Dissolution profile of formulations R1-R9

From the table it was evident that the formulation prepared with Banana Powder were showed good drug release i.e., R4 formulation (99.31%) in higher concentration of Blend i.e. 64 mg.

Formulations prepared with Primojel showed good drug release i.e., 92.12% (R8 formulation) in 64 mg concentration. When increase in the concentration of Primojel drug release was able to retarded.

Formulations prepared with Sodium starch glycolate showed maximum drug release i.e., 97.32% (R12 formulation) at 30 min in 64 mg of blend.

Among all formulations R4 considered as optimised formulation which showed maximum drug release at 30 min i.e., 99.31 %. Banana Powder showed good release when compared to other superdisintegrants. Finally concluded that R4 formulation contains Banana Powder was optimized formulation.

FTIR RESULTS:

Fig 3: FTIR of Rosuvastatin Calcium Pure Drug

Fig 4: FTIR of Rosuvastatin Calcium optimized formulation

Rosuvastatin Calcium was mixed with proportions of excipients showed no colour change providing no Drug-Excipient interactions.

CONCLUSION:

Preformulation studies of Rosuvastatin Calcium were performed, the FT-IR analysis revealed that the superdisintegrants and excipients used were compatible with Rosuvastatin Calcium. Fast dissolving tablets Rosuvastatin Calcium can be prepared by direct compression technique using superdisintegrants, namely Banana Powder, Primojel and Sodium starch glycolate. Amongst all the formulations, formulation containing Banana Powder as superdisintgrants is fulfilling all the parameters satisfactorily. It has shown excellent in vitro disintegration compared to other superdisintegrants. Apart from all the formulations of R4 formulation showed maximum drug release (99.31%) at the end of 30min. Thus, we are able to achieve our objective of preparing fast dissolving tablets of Rosuvastatin Calcium with superdisintegrants and simple method of manufacture and enhance the dissolution of the drug.

АCKNOWLEDGEMENT:

The Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе necessary facilities for the research work.

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Received on 18.02.2020 Modified on 16.03.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(2): 78-82.

DOI: 10.5958/0975-4377.2020.00014.2

Concentration (µg/mL)	Absorbance
0	0
5	0.144
10	0.288
15	0.412
20	0.552
25	0.688