Formulation and In Vitro Evaluation of Doxophylline Oral Disintegrating Tablets

 

Dr Y. Krishna Reddy*, Syed Suhaib Ahmed

Department of Pharmaceutics, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

 

ABSTRACT:

 

 

INTRODUCTION:

The oral route of administration is considered as the most widely accepted route because of its convenience of self administration, compactness and easy manufacturing. But the most evident drawback of the commonly used oral dosage forms like tablets and capsules is difficulty in swallowing, leading to patients incompliance particularly in case of pediatric and geriatric patients.¹ but it also applies to people who are ill in bed and to those active working patients who are busy or traveling, especially those who have no access to water.² Orally disintegrating tablets are appreciated by a significant segment of populations particularly who have difficulty in swallowing. It has been reported that Dysphagia. European Pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing.

 

The disintegration time for ODTs generally ranges from several seconds to about a minute.^{3,4 5}

 

The ideal characteristics of a drug for oral dispersible tablet include

·       Ability to permeate the oral mucosa.

·       Very bitter or unacceptable taste and odor drugs are unsuitable for ODT⁶

 

Desired criteria for ODTs:

·       ODT should leave minimal or no residue in mouth after oral administration, compatible with pleasing mouth feel.

·       Be portable and without fragility concern.^7,8

 

MATERIALS:

Doxofylline was Provided by Sura Labs, Dilsukhnagar, Hyderabad. Sodium starch glycolate (SSG) was purchased from S.D. Fine chemicals, Mumbai, India, Crospovidone and Microcrystalline cellulose 102 was purchased from Rubicon Research Pvt. Ltd., Mumbai, India, Ac-Di-Sol and Sodium saccharin was purchased from Merck Specialities Pvt Ltd, Mumbai, India , Talc purchased from S J Chemicals and Magnesium Stearate was purchased from Nikita Chemicals, India.

METHODOLOGY:

Table 1: Formulation table showing various compositions

Ingredients	Formulation Code
	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12
Doxofylline	400	400	400	400	400	400	400	400	400	400	400	400
Sodium starch glycolate (SSG)	20	40	60	80	-	-	-	-	-	-	-	-
Crospovidone	-	-	-	-	20	40	60	80	-	-	-	-
Ac-Di-Sol	-	-	-	-	-	-	-	-	20	40	60	80
Sodium saccharin	3	3	3	3	3	3	3	3	3	3	3	3
Talc	4	4	4	4	4	4	4	4	4	4	4	4
Magnesium stearate	4	4	4	4	4	4	4	4	4	4	4	4
Microcrystalline cellulose 102	119	99	79	59	119	99	79	59	119	99	79	59
Total weight	550	550	550	550	550	550	550	550	550	550	550	550

 

RESULTS AND DISCUSSION:

Evaluation of Pre-Compresion parameters of Powder blend:

Table 2: 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
F1	28.65±1.09	0.36±0.01	0.44±0.01	19.85±0.86	1.18±0.03
F2	27.63±0.90	0.35±0.01	0.41±0.02	18.96±0.84	1.17±0.02
F3	28.15±1.39	0.35±0.02	0.41±0.02	17.56±0.84	1.21±0.02
F4	27.20±1.39	0.35±0.02	0.43±0.02	15.28±0.36	1.16±0.03
F5	28.00±2.05	0.37±0.02	0.41±0.30	17.35±0.85	1.18±0.04
F6	28.63±1.12	0.34±0.02	0.45±0.02	18.36±1.99	1.14±0.02
F7	27.00±1.94	0.34±0.01	0.44±0.015	11.30±0.74	1.18±0.06
F8	27.54±1.55	0.36±0.01	0.41±0.02	14.55±3.16	1.17±0.03
F9	28.00±1.97	0.35±0.01	0.44±0.01	21.53±0.86	1.17±0.05
F10	28.43±0.90	0.38±0.01	0.43±0.01	17.23±1.09	1.24±0.04
F11	28.60±1.94	0.35±0.02	0.41±0.01	12.54±0.12	1.30±0.05
F12	28.52±2.37	0.34±0.02	0.42±0.015	13.52±0.11	1.58±0.13

 

·       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 0.34±0.01- 0.38±0.01 and tapped density was in the range of 0.41±0.0 -0.45±0.02 The Carr’s index and Hausner’s ratio was calculated from tapped density and bulk density.

 

Evaluations of post compression parameters of Doxofylline ODTs:

Table 3: Evaluation of post compression parameters of Doxofylline oral disintegrating tablets

Formulation codes	Average weight(mg)	Hardness (kg/cm2	Friability (%loss)	Thickness (mm)	Drug content (%)	In vitro disintegration Time (sec)
F1	549.1	5.31	0.25	4.2	98.21	48
F2	550.0	5.16	0.36	4.1	95.62	36
F3	548.6	5.92	0.58	4.8	99.14	25
F4	548.5	5.33	0.47	4.6	95.81	45
F5	549.8	5.48	0.39	4.2	99.47	26
F6	549.6	5.19	0.27	4.1	98.75	15
F7	548.1	5.92	0.12	4.7	100.0	60
F8	547.5	5.81	0.62	4.3	96.15	34
F9	545.2	5.65	0.58	4.5	99.28	29
F10	549.2	5.33	0.17	4.0	98.45	49
F11	548.9	5.48	0.24	4.8	99.84	37
F12	549.7	5.73	0.37	4.5	97.86	27

Weight variation, Thickness , Hardness, friability and Drug content all were in within limits.

 

Figure 1: In vitro disintegration Time (sec)

 

In Vitro drug release studies of Doxofylline

Table 5: Dissolution data of Doxofylline of formulations (F1-F12)

Time	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12
0	0	0	0	0	0	0	0	0	0	0	0	0
5	22.12	26.31	20.35	15.41	18.24	27.67	20.38	17.59	21.28	20.26	19.75	18.91
10	45.36	45.53	47.77	39.15	35.62	53.89	41.66	35.23	45.96	40.32	33.83	27.86
15	65. 95	62.85	63.05	60.87	54.14	67.95	57.98	48.91	63.84	55.78	47.52	42.38
20	70.42	73.15	75.12	78.98	79.39	75.91	67.97	58.67	75.37	64.91	56.86	55.94
25	73.84	84.72	76.33	89.75	85.96	88.22	82.18	71.42	88.93	74.48	65.79	67.26
30	78.96	86.48	90.95	96.21	95.49	99.57	90.88	83.61	97.69	91.75	87.12	72.31

 

Figure 2: Dissolution profile of all formulations F1-F12

 

In vitro Dissolution time:

In vitro disintegration studies showed from 5-30 minutes. The F6 formulation showed in vitro Dissolution time i.e., 30 minutes.

 

From the table it was evident that the formulation prepared with Sodium starch glycolate were showed good drug release i.e., F4 formulation (96.21%) in higher concentration of Blend i.e., 80mg. Formulations prepared with Crospovidone showed good drug release i.e., 99.57% (F6 formulation) in 40mg concentration. Formulations prepared with Ac-Di-Sol showed maximum drug release i.e., 97.69% (F9 formulation) at 30 min in 20mg of blend.

 

Among all formulations F6 considered as optimized formulation which showed maximum drug release at 30 min i.e., 99.57%. Crospovidone showed good release when compared to Sodium starch glycolate (SSG). Finally concluded that F6 formulation contains Crospovidone was optimized formulation.

 

FTIR RESULTS:

 

Figure 3: FTIR of Doxofylline pure drug

 

Figure 4: FTIR of Doxofylline optimized formulation

Doxofylline was mixed with proportions of excipients showed no colour change providing no drug-excipient interactions.

 

CONCLUSION:

In the present work, an attempt has been made to develop Oral disintegrating tablets of Doxofylline. Sodium starch glycolate (SSG), Crospovidone and Ac-Di-Sol were used to super diintegrants. The blend of all formulations showed good flow properties such as angle of repose, bulk density, tapped density. The prepared tablets were shown good post compression parameters and they passed all the quality control evaluation parameters as per I.P limits. From the Dissolution data it was evident that the formulations prepared with Sodium starch glycolate were showed good drug release i.e., 96.21 (F4) in higher concentration of blend i.e., 80mg. Formulations prepared with Crospovidone showed good drug release i.e., 99.57% (F6) in 40mg concentration , Formulations prepared with Ac-Di-Sol showed maximum drug release i.e., 97.69% (F9) Among all formulations F6 formulation was considered as optimized formulation which showed maximum drug release at 30 min i.e., 99.57%. Sodium Starch glycolate was showed good release when compared to Ac-Di-Sol. Finally concluded that F6 Formulation (containing Crospovidone) was optimized better formulation.

 

АCKNOWLEDGEMENT:

Thе Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs and drugs and excipients for thе rеsеarch work.

 

REFERENCES:

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3.      Lindgren S, Janzon L. Dysphagia; Prevalence of swallowing complaints and clinical findings. Medical clinics of North America., 1993; 77: 3-5.

4.      Fu Y, Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: Developments, technologies, taste-masking and clinical studies. Critical Review in Therapeutic Drug Carrier System. 2004;21:433-76.

5.      Brown D. Orally Disintegrating Tablets Taste over Speed. Drug Delivery Technology. 2003; 3:58-61.

6.      Kumaresan C, Orally Disintegrating Tablet - Rapid Disintegration, Sweet Taste, And Target Release Profile, Pharmainfo.net sep9 2008.

7.      Reddy L. H, Ghosh B, and Rajneesh. Fast dissolving drug delivery systems: a review of the literature. Indian Journal of Pharmaceutical Science. 2002; 64(4): 331-336.

8.      Seager H. Drug-deliver products and the zydis fast-dissolving dosage form. Journal of Pharmacy and Pharmacology. 1998;50: 375-382.

 

 

Accepted on 09.04.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(6): 2811-2814.