Formulation and Evaluation of Captopril Fast Dissolving Tablets by WOW Tab and Effervescent Technologies

Ravi Kumar*¹, Swati Patil⁴, MB Patil², Mahesh S Paschapur³ and Sachin R Patil¹

¹Dept. of Pharmaceutics, K.L.E.S’s College of Pharmacy, Ankola-581314, Karnataka, India.

²Dept. of Pharmacognosy, K.L.E.S’s College of Pharmacy, Ankola-581314, Karnataka, India.

³Dept. of Pharmacology, K.L.E.S’s College of Pharmacy, Ankola-581314, Karnataka, India.

⁴Department of Pharmacognosy, Principal KM Kundnani college of Pharmacy, Cuffe Parade, Mumbai.

ABSTRACT

Fast dissolving tablets of Captopril were prepared by Wow tab and Effervescent technologies. In this study our aim was to provide the tablet that quickly disintegrates or dissolves upon contact with saliva and also to provide a good mouth feel. The excipients used in both the technologies not only aid fast disintegration of tablets, but also mask the slight bitter taste of drug. All the prepared formulations were evaluated for thickness, hardness, friability, weight variation, drug content, and disintegration time and drug dissolution. Tablets from Wow tab and Effervescent technologies have shown 94 and 96% of the drug release at the end of 10 min respectively. Study has shown that 8:6 ratio of sodium bicarbonate and citric acid in the Captopril fast dissolving tablets gave good soothing and excellent mouth feel. Tablet prepared by Wow tab technology, formulation W5 and W6 using low moldability saccharide (lactose and mannitol) showed rapid disintegration and released about 92 and 96% drug respectively. Study concluded that fast dissolving tablets of Captopril could be prepared successfully by above mentioned methods. Tablets imparted patient benefits and increased consumer satisfaction, despite the different mechanisms involved in these techniques.

Keywords: Fast-dissolving tablets, Captopril, ACE inhibitor, oral cavity, In vitro dissolution.

INTRODUCTION

Dysphagia is seen to afflict nearly 35% of general population. Fast dissolving tablet drug delivery is rapidly gaining acceptance as an important new drug delivery technology. The concept of mouth dissolving drug delivery system emerged from the desire to provide patient with more conventional means of taking their medication. It is difficult for many patients to swallow tablets and hard gelatin capsules, which results in high incidence of non-compliance and ineffective therapy¹.

In some cases such as motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, swallowing conventional tablets may be difficult². Fast dissolving tablet when put on the tongue, disintegrates instantaneously releasing the drug. Fraction of drug is absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than that observed from conventional tablet dosage form³. The advantages of mouth dissolving dosage forms are increasingly being recognized in both, industry and academia⁴. Captopril, chemically is 1-[(2s)-3-mercapto-2 methyl propionyl]-L-proline. It is freely soluble in water, methanol and ethanol. Captopril is an angiotensin converting enzyme (ACE) inhibitor. Captopril is approved for the treatment of diabetic nephropathy^5-6, hypertension and also in the management of congestive heart failure.

Table 1: Formulation of Mouth Dissolving Tablets of Captopril by Effervescent Technology

Ingredients*	E1	E2	E3	E4	E5	E6	E7
Captopril	25	25	25	25	25	25	25
Pearlitol	142	106	114	102	106	108	102
Avicel	20	20	20	20	20	20	20
Sodium bicarbonate	-	20	16	20	24	20	16
Citric acid (anhydrous)	-	16	12	20	12	14	24
Aspartame	6	6	6	6	6	6	6
Flavor (lemon)	3	3	3	3	3	3	3
Magnesium stearate	2	2	2	2	2	2	2
Talc	2	2	2	2	2	2	2

*All quantities are expressed in mg per tablet

Table 2: Formulation of Mouth Dissolving Tablets of Captopril by Wow Tab Technique

INGREDIENTS*	W1	W2	W3	W4	W5	W6
Captopril	25	25	25	25	25	25
Mannitol	60	60	-	-	30	30
Maltose	6	-	6	-	6	-
Sorbitol	-	6	-	6	-	6
Lactose	-	-	60	60	30	30
Talc	2	2	2	2	2	2
Aspartame	4	4	4	4	4	4
MCC	10	10	10	10	10	10
Flavor( orange)	3	3	3	3	3	3

*All quantities are expressed in mg per tablet

Desired criteria for mouth dissolving drug delivery system are that it should dissolve or disintegrate in the mouth in a matter of second, have a pleasant mouth feel, compatible with taste masking, leave minimal or no residue in the mouth after oral administration, should have low sensitivity to environmental conditions, such as humidity and temperature and allow the manufacture of tablets using conventional processing and packaging equipment at low cost^7-8. Various technologies are involved in preparing mouth dissolving tablets such as freeze drying, moulding, sublimation, spray drying, wowtab, effervescent and flash tab technology.

Addition of effervescent excipients in the formulation of fast dissolving tablet is one approach for preparing fast dissolving tablets^9-12. Wow tab technology uses the combination of low and high moldability saccharides to obtain a rapidly melting strong tablets^13-14. This technology is patented by Yamonouchi Pharmaceutical Co.

EXPERIMENTAL:

Materials:

Captopril was obtained as a gift sample from Wockhardt Pharmaceuticals, Aurangabad. Talc, magnesium stearate, aspartame, Avicel was obtained from Zydus Research Centre, Ahmedabad as gift samples. All the other chemicals, solvents and reagents used were of analytical and Pharmacopoeial grade. Different instruments like a Vernier calipers, a Monsanto hardness tester, a Roche friabilator and a disintegration apparatus were supplied by Campbell Electronics, Mumbai, USP XXIII dissolution apparatus-2 was from Tab- machines, Mumbai and 1601 PC Shimadzu UV Spectrophotometer from Tokyo, Japan.

Methods:

Standard calibration curve of Captopril:

Solutions ranging from 5 to 35 µg/ml were prepared in 0.1 N HCl. Absorbance was measured at λ_max of 212 nm, using 1601 PC Shimadzu UV Spectrophotometer.

Evaluation of Blend:

Pre compression parameters:

Prior to compression into tablets, the powder blend was evaluated for pre compression properties such as Angle of repose, Bulk Density¹⁵, Tapped density, Carr’s Index, Hausner ratio¹⁶.

Characterization of drug and excipients:

Before formulating fast dissolving tablets by afore mentioned methods, the drug-excipient compatibility studies were done by using FTIR and DSC to check any compatibility related problems associated with drug and excipients used in the formulation. Mouth dissolve tablets of Captopril were prepared by the effervescent and wow tab techniques, using conventional direct compression method.

Formulation of mouth dissolving tablets by Effervescent technique:

Captopril, pearlitol, aspartame, flavor, Avicel 102, were passed through sieve no. 60. Sodium bicarbonate and citric acid were preheated at a temperature of 60⁰ C to make them anhydrous, then required quantity of each ingredient was taken for particular formulation and the blend was mixed by tumbling in a polythene bag. All the operations were carried out under controlled humidity conditions to avoid reaction between sodium bicarbonate and citric acid in the presence of moisture. The powder mixture was then compressed using 9 mm flat face punches in cadmach single punch tabletting machine under hardness of 2-3 kg/cm². The composition of each formulation is given in Table 1.

Preparation of mouth dissolving tablets by Wow tab technique:

In this technique drug was mixed with low moldability sugars like mannitol, lactose or combinations of these and granulated using high moldability sugars like maltose and lactose. After drying, the granules were blended with talc, aspartame, Avicel and flavor. The powder mixture was then compressed using 9 mm flat face punches in cadmach single punch tabletting machine, under hardness of 2-3 kg/cm². The composition of each formulation is given in Table 2.

Evaluation of tablets:

Post compression parameters:

After tablet compression, Thickness, Weight Variation, Hardness, Friability, Content uniformity, Disintegration Time¹⁷, Water absorption ratio and wetting time¹⁸. In vitro dissolution studies were carried out in USP dissolution test apparatus Type 2), using 0.1 N HCl (900ml, 37± 0.5⁰C) at 50 rpm^19-20.

Figure 1: Comparison of Disintegration time in vitro and in oral cavity of various formulations

Disintegration time in oral cavity in Seconds. Disintegration time in vitro in Seconds

Table 3: Pre Compression Parameters of Captopril Mouth Dissolving Tablets Made By Effervescent Technology

Parameters	E1	E2	E3	E4	E5	E6	E7
Bulk density (g/cc)	0.56	0.57	0.56	0.53	0.58	0.55	0.57
Tapped density(g/cc)	0.76	0.72	0.71	0.67	0.73	0.69	0.73
Bulkiness (cc/g)	1.79	1.75	1.79	1.89	1.72	1.81	1.75
Carr’s Index (%)	26.3	20.6	20.8	21.6	20.7	19.9	21.0
Hausner ratio (%)	1.35	1.26	1.27	1.26	1.26	1.25	1.28
Angle of repose(^0)	29	27	29	26	30.2	28.3	29.4

Table 4: Pre Compression Parameters of Captopril Mouth Dissolving Tablets Made By Wowtab Technology

Parameters	W1	W2	W3	W4	W5	W6
Bulk density (g/cc)	0.57	0.53	0.56	0.55	0.58	0.52
Tapped density(g/cc)	0.68	0.72	0.71	0.73	0.72	0.67
Bulkiness (cc/g)	1.75	1.85	1.76	1.80	1.70	1.89
Carr’s Index (%)	16.1	25.8	21.1	24.7	18.7	21.6
Hausner ratio (%)	1.19	1.35	1.26	1.81	1.24	1.28
Angle of repose(^0)	26.1	30.0	29.7	31.1	27.0	25.1

Table 5: Post-Compression Parameters of Captopril Mouth Dissolving Tablets Made By Effervescent Technology

Parameters	E1	E2	E3	E4	E5	E6	E7
Hardness(kg/cm^2)	3.1	2.9	3.0	3.2	2.8	3.0	3.1
Friability (%)	0.39	0.45	0.37	0.25	0.54	0.28	0.34
Thickness (mm)	3.0	32	2.9	3.1	2.8	3.0	3.2
Weight variation	6.5%
Content uniformity	98-99%

Figure 2: Comparison of Dissolution profile of various formulations of Captopril formulated by two methods with marketed product.

RESULTS AND DISCUSSION:

The IR Spectra revealed that there was no compatibility related problems between the drug and the excipients used in the formulation. Precompression parameters for the formulations prepared by effervescent and wowtab techniques are shown in Table 3 and 4 respectively. Bulk density was found to be between 0.52 to 0.58 g/cc and tapped density between 0.67 to 0.76 g/cc, bulkiness between 1.70 to 1.9. Carr’s index between 16.1 to 26.3 %, Hausner ration between 1.19 to 1.35 and angle of repose was found to be between 25 to 31⁰, indicating fair to good flow properties. The hardness of all formulations was between 3-4 kg/cm².

Table 6: Post-Compression Parameters of Captopril Mouth Dissolving Tablets Made By Wowtab Technology

Parameters	W1	W2	W3	W4	W5	W6
Hardness(kg/cm^2)	3.1	2.9	3.0	3.2	2.8	3.0
Friability (%)	0.68	0.54	0.73	0.56	0.45	0.34
Thickness (mm)	2.04	2.07	2.0.3	2.05	2.04	2.04
Weight variation	9.5%
Content uniformity	98-100%

Table 7: Comparison of Dissolution profile of various Formulations with marketed formulations

Formulations	%CDR	Formulations	%CDR
E1	30	W1	69
E2	50	W2	76
E3	90	W3	80
E4	94	W4	85
E5	86	W5	92
E6	75	W6	96
E7	70	-	--
Marketed product	85	Marketed product	85

Post compression parameters of the formulations prepared by effervescent and wowtab techniques are shown in Table 5 and 6 respectively. The friability values of all the formulations were within the limit i.e. less than 1.0. Drug content of all the formulations was found to be in the range of 98-100 %, which is within acceptable limits.

In vitro and In vivo dispersion time was 35-98 second for all the formulations. Comparison between disintegration time in oral cavity and disintegration time

(In vitro) for formulations prepared by both methods are shown in fig. 1. The In vitro dispersion time for marketed product was found to be 60 seconds.

All the designed formulations made by above methods showed rapid and percentage cumulative drug release (% CDR) at the end of 10 min is shown in Table 7, while marketed tablet of Captopril (Aceten®) showed 85% of drug release at the end of 10 min. from the data shown in table 7 it was found that the drug content in all the formulations was within the range 90-110 % of the labeled claim.

Formulations E3, E4 and W5, W6 gave increased dissolution rate than the commercial tablets.E5 and W4 gave similar dissolution rate as commercial tablets. Formulations E2, E6, E7 and W1, W2 and W3 showed less dissolution rate when compared to commercial tablets. Comparison of In vitro release profile of formulation made by two methods is shown in fig 2.

CONCLUSION:

To improve patient compliance and palatability, mouth dissolving tablets made by effervescent and wowtab technology was successfully employed for Captopril. Sodium bicarbonate and citric acid in the ration of 8:6 was found to be best for Captopril tablets made by effervescent technology. Effervescent and wowtab technologies were found to be better suited for Captopril with maximum drug release.

ACKNOWLEDGEMENTS:

The author thanks Principal, K.L.E.S’s College of Pharmacy Ankola, for providing facilities to carry out this work and to Zydus Research Center, Ahmedabad and Wockhardt Pharmaceuticals, Aurangabad for

providing gift samples of drug and excipients.

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