Preparation and Evaluation of Viloxazine Hydrochloride Bilayer Matrix Tablets

 

K. Nagasree¹*, Uppalanchi Prashanthi¹, Ramya Sri S²

¹Department of Pharmaceutics, Samskruti College of Pharmacy,

Affiliated to JNTUH University, Hyderabad 501301, Telangana, India.

²Department of Pharmacy, University College of Technology,

Osmania University, Hyderabad – 500 007, Telangana, India.

*Corresponding Author E-mail: nagasreepharmacy@gmail.com

 

 

INTRODUCTION:

Introduction of matrix tablet as Controlled release (SR) has given a new breakthrough for novel drug delivery system in the field of Pharmaceutical technology. It excludes complex production procedures such as coating and Pelletization during manufacturing and drug release rate from the dosage form is controlled mainly by the type and proportion of polymer used in the preparations.¹

Drug release through various matrix system is determined by Water penetration, Polymer swelling, Drug dissolution, Drug diffusion, Matrix erosion have been utilized as formulation sustained release drug delivery.² Matrix systems made of swellable or nonswellable polymers³.

 

Matrix devices, due to their chemical inertness, drug embedding ability and drug release character, have gained steady popularity for sustaining the release of a drug.⁴

 

Advantages of Matrix Tablets: Easy to manufacture, Versatile, and effective, It has low cost, Can be made to release high molecular weight compounds, Suitable for both non degradable and degradable systems, No danger of dose dumping in case of rupture, Can be fabricated in a wide range of sizes and shapes.⁵

 

Matrix tablet was chosen as dosage form because of cost effectiveness. The effect of various grades of HPMC on formulation parameters was evaluated.⁶

 

Matrix tablets are considered to be the commercially feasible sustained action dosage forms that involve the least processing variables, utilize the conventional facilities and accommodate large doses of drug.⁷

Matrix tablets can be defined as the oral solid dosage forms in which the drug is homogeneously dispersed or dissolved within the hydrophilic or hydrophobic polymeric matrices⁸.

 

Matrix technologies have often proven popular because of the simplicity of the manufacturing processes required, level of reproducibility, stability of the raw materials, dosage form as well as ease of scale up operation, validation and favorable in-vitro in-vivo correlation.⁹ Matrix tablets were prepared by wet granulation method using different concentration of Hydroxypropylmethylcellulose (HPMC K4M) and Ethyl Cellulose (EC) in alone and combination.¹⁰ The polymeric matrix absorbs the water and swells. Finally the drug diffusion occurs by erosion of outer surface of tablet matrix.¹¹

 

Bilayer tablets are tablets made by compressing several different granulations fed into a die in succession, one on top of another, in layers.¹² Cost of the bilayer tablets is lower compared to another oral dosages form¹³.

 

MATERIALS AND METHODS:

Viloxazine hydrochloride procured from Alkem Laboratories Ltd., Mumbai., Provided by Sura Labs, Dilsukhnagar, Hyderabad. Cros Povidone, Cross Carmellose, SSG, Kyron T 314, Ethyl cellulose, Carbopol, PVP K 30, MCC, Mg. Stearate, Talc and IPA procured from S.D. Fine Chem. Ltd. Mumbai.

 

Formulation development of Tablets:

Method of Preparation:

Direct compression was used for preparation of the immediate release layer and wet granulation technology was used for Sustained release layer containing Viloxazine hydrochloride. For both the layer, granulation was carried out separately, as follows:

 

Preparation of immediate release layer (IR):

All the ingredients were accurately weighed and passed through mesh 60#. In order to mix the ingredients thoroughly drug, superdisintegrant, microcrystalline cellulose, magnesium stearate and talc were mixed in a mortar and pestle. The powder was passed through 60# sieve and compressed on rotary tablet punching machine.

 

Preparation of sustained release layer (SR):

It was performed by wet granulation method. The required amount of sustained release polymer were blended with Viloxazine hydrochloride and passed through 80 mesh sieve. Binding solution was prepared by dissolving required amount of PVP k 30 in isopropyl alcohol (IPA).Blended powders were granulated with IPA solution and sieved using 40 mesh sieves. The granules were dried at 45˚c for 30 min in tray dryer to evaporate the IPA and then lubricated with required amount of talc, magnesium stearate, store the lubricated granules with suitable label till it’s further used.

 

Final compression of bilayer tablets:

Bilayer tablets were prepared by feeding 200 mg of SR granules manually into punch and compressed them with pre compression force. Then 100 mg of IR granules were manually fed into same die cavity SR granules and applied final compression force into rotary tablet punching machine.

 

Table 1: Composition of immediate release layer table

Immediate release layer
Ingredients (MG)	Formulation
	F1	F2	F3	F4	F5	F6	F7	F8
Viloxazine hydrochloride	100	100	100	100	100	100	100	100
Cros Povidone	10	-	-	-	20	-	-	-
Cross Carmellose	-	10	-	-	-	20	-	-
SSG	-	-	10	-	-	-	20	-
Kyron T 314	-	-	-	10	-	-	-	20
MCC	29	29	29	29	19	19	19	19
Magnesium Stearate	5	5	5	5	5	5	5	5
Talc	6	6	6	6	6	6	6	6
Total weight	150	150	150	150	150	150	150	150

 

Table 2: Composition of sustained release layer tablet

Sustained release layer
Ingredients (MG)	Formulation
	F1	F2	F3	F4	F5	F6	F7	F8
Viloxazine hydrochloride	100	100	100	100	100	100	100	100
Ethyl cellulose	25	50	75	100	-	-	-	-
Carbopol	-	-	-	-	25	50	75	100
PVP K 30	10	10	10	10	10	10	10	10
MCC	154	129	104	79	154	129	104	79
Mg. Stearate	5	5	5	5	5	5	5	5
Talc	6	6	6	6	6	6	6	6
IPA	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S
Total weight	300	300	300	300	300	300	300	300

All the quantities were in mg

RESULTS AND DISCUSSION

Analytical Method

Graphs of Viloxazine hydrochloride were taken in 0.1N HCl and in pH 6.8 phosphate buffer at 221 nm and 225 nm respectively.

 

Figure 1: Standard graph of Viloxazine hydrochloride in 0.1N HCl

 

Figure 2: Standard graph of Viloxazine hydrochloride pH 6.8 phosphate buffer (228 nm)

 

 

For IR Formulation:

Preformulation parameters of powder blend:

Table 3: Pre compression study of immediate release layer tablets

Formulation Code	Angle of Repose	Bulk density (gm/ml)	Tapped density (gm/ml)	Carr’s index (%)	Hausner’s Ratio
F1	26.05±0.65	0.307	0.444	13.46	1.16
F2	25.94±0.56	0.384	0.434	17.85	1.22
F3	26.02±0.61	0.267	0.307	13.33	1.15
F4	26.21±0.93	0.346	0.404	14.35	1.16
F8	26.28±0.33	0.323	0.376	14.09	1.16
F6	25.81±0.61	0.393	0.453	13.24	1.15
F7	26.10±0.53	0.318	0.368	13.58	1.16
F8	26.21±0.32	0.312	0.358	12.84	1.15

 

Table 4: Post compression study for IR tablet

Formulation codes	Weight variation (mg)	Hardness (kg/cm2)	Friability (%loss)	Thickness (mm)	Drug content (%)	Disintegration time of IR tablets (seconds)
F1	146.14	4.9	0.17	3.14	98.44	45
F2	150.12	4.3	0.35	3.64	99.72	31
F3	147.58	3.9	0.61	3.98	98.34	25
F4	150.01	4.7	0.47	3.62	96.34	20
F5	147.36	3.8	0.50	3.09	98.14	38
F6	149.57	4.5	0.37	3.14	99.92	16
F7	148.37	4.7	0.30	3.27	97.21	26
F8	150.18	4.0	0.19	3.63	95.37	20

Table 5: In vitro dissolution study of immediate release tablets

Time (minutes)	Cumulative % Drug release
	F1	F2	F3	F4	F5	F6	F7	F8
0	0	0	0	0	0	0	0	0
10	39.22	41.33	43.88	49.22	47.55	43.55	38.22	42.66
20	48.59	52.71	55.38	63.58	61.9	57.40	46.33	54.33
30	61.17	65.31	69.44	73.75	66.27	64.06	59.72	71.27
45	72.31	76.46	78.05	86.52	82.89	75.34	71.11	83.61
60	86.33	89.60	91.75	94.97	96.33	98.35	89.88	93.57

 

Tablet powder blend was subjected to various pre-formulation parameters. The angle of repose values indicates that the powder blend has good flow properties. The bulk density of all the formulations was found to be in the range of   0.267 to 0.393 (gm/cm³) showing that the powder has good flow properties. The tapped density of all the formulations was found to be in the range of 0.307 to 0.453 showing the powder has good flow properties. The compressibility index of all the formulations was found to be below 17.85 which show that the powder has good flow properties. All the formulations has shown the hausner ratio below 1.22 indicating the powder has good flow properties.

 

Quality Control parameters for tablets:

Tablet quality control tests such as weight variation, hardness, and friability, thickness, and drug release studies in different media were performed on the compression coated tablet.

 

The disintegration time of the IR tablets ranged from 45 seconds to 16 seconds.  The disintegration time of the IR tablets containing 20mg Cross Carmellose was found to have optimum disintegration time (16 seconds) for IR tablets.

 

Fig 3: In vitro dissolution study of IR tablets of Viloxazine hydrochloride

 

The in vitro dissolution study of IR tablets showed that concentration of 20mg Cross Carmellose was found to be optimum for immediate release of Viloxazine hydrochloride. The 20mg concentration of Cros Povidone was found to be releasing the drug slowly when compared to SSG. The 20mg concentration of Cros Povidone released 98.35% at the end of 30minutes. Therefore formulation F6 was optimized and selected for final bilayer tablets.

 

Tablet powder blend was subjected to various pre-formulation parameters. The angle of repose values indicates that the powder blend has good flow properties. The bulk density of all the formulations was found to be in the range showing that the powder has good flow properties. The tapped density of all the formulations powders has good flow properties. The compressibility index of all the formulations was found to be below 17.99 which show that the powder has good flow properties. All the formulations have shown the hausner ratio below 1.214 indicating the powder has good flow properties.

 

All the parameters such as weight variation, friability, hardness, thickness and drug content were found to be within limits.

 

 

For IR Formulation

Table 6: Pre compression study of sustained release layer tablets

Formulation code	Angle of repose (Ө)	Bulk density (gm/cm3	Tapped density(gm/cm3)	Carr’s index (%)	Hausner’s ratio
F1	28.46	0.5710	0.6897	17.21	1.121
F2	28.48	0.5698	0.6701	14.96	1.176
F3	28.46	0.5725	0.6909	17.14	1.206
F4	28.40	0.5702	0.6782	15.92	1.189
F5	28.71	0.5620	0.6787	17.99	1.207
F6	28.70	0.5602	0.6698	17.11	1.196
F7	28.65	0.5562	0.6714	16.36	1.207
F8	28.80	0.5665	0.6813	16.85	1.203

All the values represent n=3

 

Table 7: Post compression study for SR tablet

Formulation codes	Weight variation (mg)	Hardness (kg/cm2)	Friability (%loss)	Thickness (mm)	Drug content (%)
F1	449.36	5.1	0.86	5.15	97.14
F2	447.25	5.5	0.64	5.69	99.10
F3	447.62	5.7	0.53	5.14	98.42
F4	450.04	5.9	0.42	5.55	97.21
F5	448.12	5.0	0.54	5.20	99.43
F6	446.74	5.2	0.45	5.48	98.74
F7	448.37	5.9	0.36	5.92	96.45
F8	449.86	6.0	0.24	5.48	98.52

 

 

In-Vitro Drug release studies

 

Table 8: Dissolution data of Viloxazine hydrochloride tablets

TIME (H)	CUMULATIVE % OF DRUG RELEASE
	F1	F2	F3	F4	F5	F6	F7	F8
0	0	0	0	0	0	0	0	0
1	18.63	13.27	8.90	10.22	10.14	7.27	8.94	7.52
2	29.55	16.75	12.83	15.93	14.65	14.76	16.52	19.14
3	35.84	22.41	17.94	18.51	25.93	29.28	20.54	27.92
4	40.39	26.39	19.30	23.74	37.35	38.64	24.13	37.63
5	46.71	29.56	22.46	29.93	43.72	50.71	34.24	45.25
6	54.05	32.81	25.62	34.45	52.72	54.72	48.15	59.25
7	61.87	38.40	32.76	38.60	63.91	69.36	52.53	67.55
8	67.02	42.52	37.61	45.91	74.22	72.33	61.86	70.24
9	75.12	48.75	45.85	47.59	83.18	81.46	74.95	74.73
10	82.21	56.16	50.96	56.75	89.24	88.76	79.74	81.63
11	89.50	73.39	62.35	60.32	91.74	90.85	86.53	84.95
12	98.14	85.54	78.14	66.83	99.43	93.96	91.62	89.85

The results of In vitro dissolution study of SR tablets showed that

The formulation F1-F4 containing Ethyl cellulose had released the drug 98.14% in 12 hours.

The formulation F5-F7 containing Carbopol (25mg) had released the drug 99.43% in 12 hours.

Based on the comparative release profile, formulation F5 was selected for the final bilayer tablets.

 

In vitro Dissolution Study of Viloxazine Hydrochloride In Bilayer Tablet

 

Fig 4: In vitro dissolution study of Viloxazine hydrochloride in bilayer tablet

 

Application of Release Rate Kinetics to Dissolution Data:

Various models were tested for explaining the kinetics of drug release. To analyze the mechanism of the drug release rate kinetics of the dosage form, the obtained data were fitted into zero-order, first order, Higuchi, and Korsmeyer-Peppas release model.

 

Fig 5: Zero order release kinetics graph

 

In Higuchi diffusion kinetics the R² value was near to 1. So it was concluded that the optimized formulation follows Zero order release kinetics mechanism.

Drug – Excipient compatibility studies

Fourier Transform-Infrared Spectroscopy:

 

CONCLUSION:

Success of the in vitro drug release studies recommends the product for the further In vivo studies, which may improve patient compliance.

 

Viloxazine hydrochloride potentiates the effect of Neurodevelopmental disorders. Hence the bilayer tablets of Viloxazine hydrochloride were used to improve patient compliance towards the effective management Attention deficit hyperactivity disorder (ADHD).

 

From the results, formulated bilayer tablet provides better in vitro release from immediate release layer as well as sustained release layer.

 

From the results, formulated bilayer tablet provides better in vitro release from immediate release layer as well as sustained release layer.

 

ACKNOWLEDGEMENT:

Thе Authors arе thankful to Principal, Department of Pharmacy, Samskruti College of Pharmacy, Hyderabad, for extending the support to carry out the research work. Finally, the authors express their gratitude to the Sura Labs, Dilsukhnagar, Hyderabad, for providing research equipment and facilities.

 

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Received on 08.10.2022                    Modified on 07.11.2022

Accepted on 25.11.2022                   ©AJRC All right reserved