Formulation and In Vitro Evaluation of orally Disintegrating Tablets of Amlodipine Besylate

 

Dr. Y. Krishna Reddy¹*, Gopagoni lavanya²

^1,2 Department of Pharmaceutics, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

 

ABSTRACT:

The present study was carried out to Develop Oral Disintegration Tablets of Amlodipine Besylate. Crospovidone, Cros carmellose sodium and Fenugreek were used as Super Disintegrants. The blend of all the 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. Among all the formulations F4 showed maximum % drug release i.e., 99.44 % in 45 min hence it is considered as optimized formulation

 

 

INTRODUCTION:

Formulation of drugs into a presentable form is the basic requirement and need of today. Dosage form is a mean of drug delivery system, used for the application of drug to a living body. Various type of dosage forms are available such as tablets, syrups, suspensions, suppositories, injections, transdermal and patches having different type of drug delivery mechanisms. These classical/modern dosage forms have some advantages and disadvantages therefore the development of an ideal drug delivery system is a big challenge to the pharmacist in the presence scenario. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. For the development of a suitable dosage form a thorough study about the physicochemical principles that governs a specific formulation of a drug should be subjected ¹.

 

During establishing dosage form for a drug, it requires knowledge about each ingredient i.e. physical, chemical and biological properties along with the compatibility with the active drug, so that the product formed should be palatable, stable and efficacious. Most drugs pass through the barrier by molecular diffusion, or through pores called pore diffusion. In pore diffusion the drug release rate is controlled by the crystal size, molecular size, pore size, pore structure and tortuosity of the polymers. In passive transport (Fick's first law) the drug moves from high concentration to the low concentration, while in active transport energy is required for the movement of drug from low to high concentration region through one or more transport mechanisms. It requires energy or carrier such as enzyme, protein ².

 

Need of Innovative Drug Delivery System:

The orally administered drug delivery is still considered as a standard system in pharmaceutics field and still considered safest, convenient and economical method of administration providing best route for patient compliance ³, however in case of tablet and capsule having a common drawback of difficulty in swallowing leading to poor compliance specially in geriatrics ⁴.

 

 

To improve compliance and making the administration convenient, design of new dosage forms gained significant importance. Conventional oral drug delivery present a drug with quick and full release that may go as such without producing the desired effect may be due to the presence of food, pH of the stomach, enzymatic degradation, change in GIT motility as so forth, giving not enough time to get absorbed ⁵. Recently much light is being put on the area of designing drug delivery systems bearing organoleptic elegancy and maximum patient acceptability in pediatrics and geriatric groups ^{6,7 8}. A lot of innovative work is being done on drug delivery in which oral route is preferred because of ease of administration, cost effective therapy, self medication and noninvasive method leading to patient compliance to a higher level. Tablet coating is one of the parameter in drug delivery designing applied to minimize the bad tasting and side effects while enhancing elegancy and drug bioavailability ⁹.

 

AIM AND OBJECTIVE:

Aim:

The aim of the present study is to formulate Amlodipine Besylate Oral disintegrating tablets.

 

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 oral disintegrating tablets (ODTs) which has gained acceptance and popularity in the recent times.

 

The prime factor for the commercial success of oral disintegrating 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 Amlodipine Besylate.

 

MATERIALS AND METHOD MATERIALS:

Amlodipine Besylate was Provided by SURA LABS, Dilsukhnagar, Hyderabad. Crospovidone Cros carmellose sodium, Fenugreek, Talc, Magnesium Stearate, Mannitol was Purchased from Merck Specialities Pvt Ltd, Mumbai, India

 

METHODOLOGY:

Formulation development:

·       Drug and different concentrations of super disintegrants (Cross caramellose Sodium, Cross povidone, Fenugreek) and required ingredients were accurately weighed and passed through a 40-mesh screen to get uniform size particles and mixed in a glass motor for 15 min.

·       The obtained blend was lubricated with magnesium stearate and glidant (Talc) was added and mixing was continued for further 5 min.

·       The resultant mixture was directly compressed into tablets by using punch of rotary tablet compression machine. Compression force was kept constant for all formulations.

 

Table: Formulation table showing various compositions

Ingrediants	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12
Amlodipine Besylate	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5	2.5
Crospovidone	5	10	15	20	-	-	-	-	-	-	-	-
Cros carmellose sodium	-	-	-	-	5	10	15	20	-	-	-	-
Fenugreek	-	-	-	-	-	-	-	-	5	10	15	20
Talc	5	5	5	5	5	5	5	5	5	5	5	5
Magnesium stearate	5	5	5	5	5	5	5	5	5	5	5	5
Mannitol	82.5	77.5	72.5	67.5	82.5	77.5	72.5	67.5	82.5	77.5	72.5	67.5
Total Weight	100	100	100	100	100	100	100	100	100	100	100	100

 

RESULTS AND DISCUSSION:

Preparation of calibration curve of Amlodipine Besylate:

The regression coefficient was found to be 0.999 which indicates a linearity with an equation of y=0.029 x-0.010. Hence Beer-Lmbert’s law was obeyed.

 

 

 

 

Table: Calibration curve data of Amlodipine Besylate in pH 6.8 phosphate buffer

Concentration	Absorbance
0	0
5	0.168
10	0.315
15	0.458
20	0.599
25	0.756

 

FIG: Calibration curve data of Amlodipine Besylate in pH 6.8 phosphate buffer

 

·       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±0.01and tapped densiy was in the range of 0.41±0.02 - 0.45±0.02

 

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

Evaluation of Pre-Compresion Parameters of Powder Blend

Table: 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	27.54±1.55	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

 

Evaluations of Post Compression Parameters of Amlodipine Besylate Odts

Table: Evaluation of post compression parameters of Amlodipine Besylate Fast dissolving tablets

Formulation codes	Average weight(mg)	Hardness (kg/cm2	Friability (%loss)	Thickness (mm)	Drug content (%)	In vitro disintegration Time(sec)
F1	98.12	3.12	0.54	2.23	99.16	26
F2	99.56	3.24	0.46	2.25	97.38	18
F3	97.17	3.10	0.48	2.19	98.76	22
F4	100.02	3.34	0.32	2.16	97.03	12
F5	96.14	3.41	0.65	2.27	99.74	35
F6	98.59	3.30	0.49	2.18	99.91	42
F7	99.19	3.24	0.40	2.24	97.26	34
F8	97.34	3.43	0.42	2.22	98.86	52
F9	97.28	3.25	0.51	2.25	98.54	32
F10	99.74	3.39	0.47	2.17	96.63	46
F11	98.69	3.45	0.52	2.26	97.71	14
F12	99.11	3.10	0.48	2.28	98.24	27

 

Weight variation and Thickness:

All the formulations were evaluated for uniformity of weight using electronic weighing balance and the results are shown above. The average tablet weights of all the formulations were noted down.

 

Hardness and friability:

All the ODT formulations were evaluated for their hardness using Monsanto hardness tester and the results are shown above. The average hardness for all formulations was found to be between (3.10 -3.45) kg/cm² which was found to be acceptable. Friability was determined to evaluate the ability of the tablets to with stand the abrasion during packing, handling and transpoting. All the ODT formulations were evaluated for their percentage friability using Roche friabilator and the results are shown above. The average percentage friability for all the formulations was between 0.32 - 0.65 which was found to be within the limit.

 

Drug content:

All formulations were evaluated for drug content according to the procedure described in methodology section and the results were shown above. The assay values for all formulations were found to be in the range of (96.63 -99.91). According to IP standards the tablets must contain not less than 95% and not more than 105% of the stated amount of the drug. Thus, all the ODT formulation comply with the standards given in IP.

 

In vitro Disintegration time:

In vitro disintegration studies showed from 12-52 sec. The F4 formulation showed in vitro Disintegration time i.e 12 sec.

 

Figure: In vitro disintegration Time(sec)

 

In Vitro Drug Release Syudies of Amlodipine Besylate

Table: Dissolution data of Amlodipine Besylate

Time (Min)	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	28.62	32.76	37.23	43.08	38.98	35.63	31.86	27.64	25.44	33.67	38.15	34.84
10	35.11	43.18	49.89	57.99	54.75	52.64	48.15	42.75	38.79	45.93	52.83	46.62
15	48.89	54.33	61.93	69.79	63.23	58.25	53.48	49.36	46.67	53.18	58.48	55.76
20	56.75	63.59	71.52	77.26	75.61	68.14	64.09	58.26	62.48	69.64	73.69	62.57
30	72.35	78.19	82.87	90.38	86.48	81.36	76.29	66.37	74.29	71.98	79.23	75.46
45	81.22	87.01	93.79	99.44	97.86	94.24	91.83	85.79	92.48	86.07	82.16	74.83

 

Fig: Dissolution profile of formulations F1- F4

 

Fig: Dissolution profile of formulations F5-F8

Fig: Dissolution profile of formulations F9-F12

 

Fig: Dissolution profile of all formulations F1-12

 

From the table it was evident that the formulation prepared with Crospovidone were showed good drug release i.e., F4 formulation (99.44%) in higher concentration of Blend i.e 20 mg. Formulations prepared with Cros carmellose sodium showed good drug release i.e., 97.86 % (F5 formulation) in 5 mg concentration. When increase in the concentration of Cros carmellose sodium was un able to retarded drug release. Formulations prepared with Fenugreek showed maximum drug release i.e., 92.48 % (F9 formulation) at 45 min in 5 mg of blend.

 

Among all formulations F4 considered as optrimised formulation which showed maximum drug release at 30 min i.e., 99.44 %. Cros carmellose sodium showed good release when compared to Fenugreek. Finally concluded that F4 formulation contains Crospovidone was optimized formulation.

 

FTIR RESULTS:

 

Fig: FTIR of Amlodipine Besylate Pure Drug

 

Fig: FTIR of Amlodipine Besylate optimized formulation

 

Amlodipine Besylate 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 Amlodipine Besylate. Crospovidone, Cros carmellose sodium and Fenugreek were used to super disintegrants. 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 Crospovidone were showed good drug release i.e., 99.44 (F4) in higher concentration of blend i.e., 20 mg. Formulations prepared with Cros carmellose sodium showed good drug release i.e., 97.86 % (F5) in 5mg concentration, Formulations prepared with Fenugreek showed maximum drug release i.e., 92.48 % F9) Among all formulations F4 formulation was considered as optimized formulation which showed maximum drug release at 30 min i.e., 99.44 %. Cros carmellose sodium was showed good release when compared to Fenugreek. Finally concluded that F4 Formulation (containing Crospovidone) was optimized better formulation.

 

АCKNOWLEDGEMENT:

Thе Authors Arе Thankful to Sura Labs, Dilshukhnagar, Hydеrabad For Providing Thе Nеcеssary Facilitiеs For Thе Rеsеarch Work.

 

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Received on 11.11.2019         Modified on 30.11.2019

Accepted on 18.12.2019       ©A&V Publications All right reserved