Assessment and In Vitro Release Profiles of Salbutamol Sulphate from Hypromellose and Carbomer Based Matrix Tablets

 

Kanij Fatema¹, Md. Zakiur Rahman², Tasnuva Haque^1*, Muhammad Shahidul Islam¹ and Sayma Ara Dayna¹

¹Department of Pharmacy, Stamford University Bangladesh, 51 Siddeswari Road, Dhaka-1217, Bangladesh

²Department of Pharmacy, East West University Bangladesh,

*Corresponding Author E-mail: Shoume_du@yahoo.com

ABSTRACT:

In the present study an effort has been made to evaluate the effect of hydrophilic polymer as a rate retarding material to sustain the release of Salbutamol Sulphate from the sustained release tablet. Formulation of salbutamol sulphate sustained release tablet were made by direct compression method, using hypromellose 15,000 cps, hypromellose 4000 cps and carbomer 934P as release rate controlling polymer. These polymers were used at different concentration. Physical parameters of the prepared tablets were evaluated. To find out the appropriate dissolution media upon solubility, different media (distilled water, 0.9% NaCl, 0.1 N HCl, Phosphate buffer) were used for preparation of standard solution and dissolution media. The maximum absorbance was observed at 276nm for each preparation using UV-Visible spectroscopy. Release profile of sulbutamol sulphate from this sustained release tablet at dissolution media (pH-7.4 phosphate buffer) was investigated using USP apparatus-II paddle method for eight hours and the drug content was measured by UV-Visible Spectroscopy. The release rate, extent and mechanisms were found to be governed by polymer type and their content. Highly viscous and higher content of hypromellose 15,000 cps (40%) in the F-3 was shown comparatively slower rate and extent of drug release than other formulations. The release mechanism was explored and explained with Zero order, Higuchi, First order and Korsmayer equation. Release profile of sulbutamol sulphate from F-1, F-2 F-3, F-5, F-6, F-7, F-8, F-9, F-10, F-11 and F-12 showed a tendency to follow Zero order Kinetics. F-1, F-2 F-3, F-4, F-7, F-8, F-9, F-10 and F-13 followed Higuchi Kinetics. Most of the formulations follow non-Fickian (anomalous) release except F-7, F-8, F-10, F-11, and F-13 which show Fickian (Case І) release. The higher MDT value of F-3 indicates a higher drug retaining ability of Hypromellose 15,000 cps. Two market preparations were taken to compare release profile with the prepared tablets. Result showed that tablet formulated with hypromellose 15000 cps exit sustaining effect comparatively better than market preparation.

 

 

INTRODUCTION:

Sustained release dosage forms are drug delivery systems that are designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. It provides an initial sufficient amount of drug to cause a rapid onset of desired therapeutic responses and an additional amount of drug that maintain the response at the initial level for a desired number of hours beyond the activity resulting from conventional dose.¹

 

Salbutamol is a β₂-adrenoceptor agonist which stimulates b-adrenergic receptors. The main effect following oral administration of salbutamol is bronchodilation resulting from relaxation of smooth muscles of the bronchial tree. Results of animal studies indicate that salbutamol does not cross the blood brain barrier, but the drug apparently crosses the placenta. It is extensively metabolized in the liver mainly to salbutamol 4-o-sulphate which has little or no b-adrenergic blocking effect. Salbutamol and its metabolites are rapidly excreted in urine and faeces. The plasma half-life of salbutamol following aerosol or oral administration is between 2.7 to 5 hours. It is indicated for the relief of bronchospasm in patients with reversible obstructive airway diseases like Bronchial asthma, chronic bronchitis, Emphysema, etc. The most frequent adverse reactions to salbutamol are nervousness, tremor, headache, tachycardia, and palpitation. For salbutamol SR, usual dose is one 8 mg tablet twice daily or as prescribed by physicians.²

Hydroxypropyl methylcellulose (HPMC) is a semisynthetic, inert, viscoelastic polymer which has been used as an ingredient to delay the release of a medicinal compound into the digestive tract. carbomer 934P is a high molecular weight polymer of acrylic acid cross-linked with allyl ethers of sucrose or pentaerythritol which was also a release rate controlling polymer.³

 

Oral sustained release dosage form by direct compression technique is a very simple approach of drug delivery systems that proved to be rational in the pharmaceutical arena for its ease, compliance, faster production, avoid hydrolytic or oxidative reactions occurred during processing of dosage forms.⁴

 

Sustained or controlled drug delivery occurs while embedded within a polymer that may be natural or semi-synthetic or synthetic in nature. The polymer is judiciously combined with the drug or other active ingredients in such a way that the active agent is released from the material in a predetermined fashion and released the drug at constant rate for desired time period.⁵

 

The matrix tablet by direct compression has attracted much attention due to its technological simplicity in comparison with other controlled release systems. Direct compression method has been applied for preparation of tablet matrix that involved simple blending of all ingredients used in the formulations and then underwent direct compression. It required fewer unit operations, less machinery, reduced number of personnel and reduced processing time, increased product stability and faster production rate.⁶

 

A wide array of polymers has been employed as drug retarding agents each of which presents a different approach to the matrix concept. Polymers that primarily forming insoluble or skeleton matrices are considered as the first category of retarding materials and are classified as plastic matrix systems. The second class represents hydrophobic and water-insoluble materials, which are potentially erodable and the third group exhibits hydrophilic properties. There are three primary mechanisms by which active agents can be released from a delivery system: diffusion, degradation, and swelling followed by diffusion. The release of drug from the tablet matrix depends on the nature of polymer. Hypromellose and carbomer are hydrophilic polymer that becomes hydrated, swollen and facilitates to diffuse the drug.⁷

 

Materials and Methods:

Materials: Sulbutamol Sulphate was a gift sample of Eskayef Bangladesh Ltd. Other materials used throughout the experiment were Hypromellose 15,000 cps [BASF (BD) Ltd.], Hypromellose  4,000 cps [BASF (BD) Ltd.], Carbomer 934P  (Colorcon Limited, India), kollidon K-30 (BASF, U.S.A), Microcrystalline Cellulose, Lactose, Colloidal Silicon Dioxide, Magnesium Stearate (Hanau Chemicals Ltd., Japan)

 

Reagents: tribasic sodium phosphate, and hydrochloric acid (37%), Potassium Dihydrogen Phosphate, 0.9% NaCl, Hydrochloric Acid (Merck, Germany)

 

Instruments: UV Spectrophotometer (HACH DR/4000U, USA), dissolution tester (Pharmatest, Germany), a tablet compression machine (Drug machineries, India), tablet testing machine (Pharmatest, Germany) and Friability tester (Pharma test, Germany)

 

Preparation of 0.9% NaCl Solution:

9.0g of Sodium Chloride (NaCl) was taken into a 1-liter volumetric flask, dissolved in and diluted up to the mark with distilled water. This solution is known as 0.9% NaCl solution.

 

Preparation of 0.1 N HCl:

9.8 ml of 37% Hydrochloric acid was taken into a 1-liter volumetric flask, dissolved in and diluted up to the mark with distilled water. The concentration of this solution is 0.1 N.

 

Preparation of Phosphate Buffer (pH-7.4):

27.22g of monobasic Potassium Phosphate (KH₂PO₄) was dissolved in water and dilute with water up to 1000 ml. The concentration of this solution was 0.2 M. 50 ml of this solution was placed in a 200 ml volumetric flask; add 39.1 ml of 0.2M sodium hydroxide and finally the volume was made 200 ml with distilled water.

 

Preparation of tablets by direct compression:

For tablet preparation, method of dry blending of the active ingredients with polymers, diluent, lubricant and glidant followed by direct compression was followed. The active ingredient and other excipients were accurately weighted for fifty tablets according to the formulations. Properly weighed hypromellose or carbomer, microcrystalline cellulose, lactose, povidone K-30, magnesium stearate, colloidal silicon dioxide and the active ingredient were then taken in a photo film container and blended in a laboratory designed small drum blender machine for about 30 minutes. Particular attention has been given to ensure thorough mixing and phase homogenization. The appropriate amounts of the mixture were accurately weighted in an electronic balance for the preparation of each tablet and finally compressed. Before compression, the surfaces of the die and punch were lubricated with magnesium stearate and taken in a single punch machine equipped with 6 mm diameter die and punch. Finally the tablets were prepared.

 

Evaluation of Tablets:

Hardness and tensile strength:

Ten tablets of each of the formulations were taken and hardness was measured by Hardness tester. The average value was calculated and the testing unit was kp. Measurement of tensile strength was conducted in the axial and radial directions with the intact matrix discs according to Fell and Newton (equation 1 and 2):

T_axial = 4F/ (ПXD²)…………………….. (1)

T_radial = 2F/ (ПXDXH)…………………. (2)

Where F, D and H are the crushing force (kp), diameter (mm) and thickness (mm) of the tablets.

 

Thickness Measurement:

Ten tablets of each of the formulations were taken and thickness was measured. The values were reported in millimeter (mm). Mean was calculated.

 

Diameter Measurement:

Ten tablets of each of the formulations were taken and diameter was measured. The values were reported in millimeter (mm). Mean was calculated.

 

Friability Test:

Ten tablets of each of the formulations were weighed out and taken into the rotating disk of a Friability tester. It was allowed to rotate at 25 rpm for 4 minutes. At the end of the rotation, tablets were collected, dedusted and reweighed. The friability was calculated as the percent of weight loss.

 

Wavelength selection:

In UV-Visible Spectrophotometer the wavelength of Salbutamol Sulphate was scanned in different media and in every media it show peak maxima at 276 nm.

 

Drug content assay:

To determine the drug content uniformity 10 tablets from each formulation were triturated. Weight of individual tablet was measured and takes the same weight from the triturated powder in 100 ml volumetric flask. 5 ml Phosphate Buffer was then added into it to dissolve in and diluted up to the mark with pH- 7.4 Phosphate Buffer. Then the solutions were scanned in UV- Visible spectrophotometer and for each value of absorbance, the concentration of the corresponding solution was calculated by using equation of the standard curve.

 

In vitro release studies:

The dissolution of prepared Salbutamol Sulphate SR tablets was monitored using standard USP 23 apparatus II (paddle) equipment and UV-Visible spectrophotometer at 276 nm. The dissolution test was performed using 500ml distilled water/Phosphate buffer/0.9% NaCl at 37°C± 0.5^oC and 50 rpm. At every 1 hour interval samples of 10ml were withdrawn from the dissolution medium and that amount was replaced with fresh medium to maintain the volume constant. The samples were filtered through a Whatman filter paper. The absorbance of the solutions was measured at 276 nm for drug salbutamol sulphate by using a UV-spectrophotometer. Percentage of drug release was calculated using an equation obtained from the standard curve. The dissolution study was continued for 8 hours to get a simulated picture of the drug release in the in-vivo condition and drug dissolved at specified time periods was plotted as percent release versus time (hours) curve.

 

Release kinetics:

The suitability of several equations that are reported in the literature to identify the mechanisms for the release of salbutamol sulphate was tested with respect to the release data. The data were evaluated according to the following equations:

Zero-order model: ⁸

               M_t = M₀ + K₀t ………………… (3)

 

Higuchi model: ^9,10

               M_t = M₀ + K_Ht^0.5 ……………….. (4)

 

Korsmeyer-Peppas model: ^11,12

               M_t = M₀ + K tⁿ ………………... (5)

Where, M_t is the amount of drug dissolved in time t, M₀ is the initial amount of drug, K₀ is the zero-order release constant, K_H is the Higuchi rate constant, K is a release constant, and n is the release exponent that characterizes the mechanism of drug release.

 

First order model: ¹³

               LogC = LogCo – kt/2.303…………………. (6)

Where, C = cumulative percent of drug release, Co = the initial concentration of drug and k = first order rate constant.

 

The magnitude of the exponent n explains the release mechanisms showed in Table-2. ¹⁴

 

Due to the differences in drug release kinetics, the constant k, though one of the measures of release rate, should not be used for comparison. Therefore, to characterize the drug release rates in different experimental conditions, mean dissolution time (MDT) was calculated from dissolution according to Mockel and Lippold¹⁵ using the following equation:

MDT = n X (K^-1/n)/ (n+1)……………. (7)

Where n is the release exponent and K is the kinetic constant calculated from Equation 7.

 

…….. (8)

 

Where, R_t and T_t are the percentage of drug dissolved at each time point for the test and reference products, respectively and n is the number of dissolution samples taken The US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products have suggested that two dissolution profiles can be considered similar if f₂ is between 50 and 100.¹⁶

 

RESULTS:

The average diameter and thickness of the tablets ranged from 6.41 to 6.43 mm and 3.21 to 3.24 mm respectively. The average % deviation of 10 tablets of each formula was less than ± 0.03. The average hardness, axial tensile strength and radial tensile strength were from 3.10 to 3.50 kp, 0.095 to 0.108 kp and 0.095 to 0.107 kp respectively. The average % friability was from 0.10 to 0.40. Drug content of the thirteen formulations ranged from 99.62 to 99.85 % (Table-3).

 

Table 1: Formulation of hypromellose and carbomer 934P based salbutamol sulfate matrix tablets

Ingredients	Formulations
	F-1	F-2	F-3	F-4	F-5	F-6	F-7	F-8	F-9	F-10	F-11	F-12	F-13
	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)	(mg)
Salbutamol Sulphate	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64	9.64
Hypromellose 15,000 cps	20	30	40	20	30	40	_	_	_	_	_	_	_
Hypromellose 4,000 cps	_	_	_	_	_	_	20	30	40	20	30	40	_
Carbomer 934 P	_	_	_	_	_	_	_	_	_	_	_	_	20
Microcrystalline Cellulose	20	20	20	30	30	30	20	20	20	30	30	30	20
Lactose	48	38	28	38	28	18	48	38	28	38	28	18	48
Povidone K-30	5	5	5	5	5	5	5	5	5	5	5	5	5
Magnesium Stearate	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5
Colloidal Silicon Dioxide	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5

 

 

Fig. 1: Standard Curve for salbutamol sulphate in phosphate buffer

 

After preparing the tablets with hypromellose 15000 cps different concentration in F-1 (20%), F-2 (30%), F-3 (40%) and their dissolution studies were performed. Six tablets from each formulation were used in each dissolution study and the release pattern of salbutamol sulphate was monitored up to eight hours. In F-4, F-5 and F-6 the amount of microcrystalline cellulose and lactose were changed. In these formulations, 30% microcrystalline cellulose was used. The percentage of drug release of these six formulations was obtained from the dissolution studies at different time intervals and zero order kinetic plots of these formulations are shown in Figure 2.

 

After 8 hours the total percent release of salbutamol sulphate from F-1, F-2, and F-3 was 99.46%, 98.60% and 96.60%. So, it was observed that drug release rate has been significantly decreased with increasing the amount of hypromellose 15000 cps. After 8 hours the total percent release of salbutamol sulphate from F-4, F-5 and F-6 was 99.86%, 99.16% and 98.34%. So, it was observed that changing the amount of microcrystalline cellulose and lactose showed change in percent release. The release rate is more controlled in F-3 where 30% hypromellose 15000 cps is used with 20% microcrystalline cellulose.

 

Fig.2: Cumulative percent release vs. time curve of hypromellose 15, 000 cps based matrix tablets

 

After preparing the tablets with hypromellose 4,000 cps as rate controlling polymer at different concentration in F-7 (20%), in F-8 (30%), and in F-9 (40%) was used. In F-10, F-11 and F-12 the amount of microcrystalline cellulose and lactose were changed. In these formulations, 30% microcrystalline cellulose was used where as 20% percent of this polymer was used. The percentage of drug release of these six formulations was obtained from the dissolution studies and zero order kinetic plots of these formulations shown in Figure 3.

 

After 6 hours the total percent release of salbutamol sulphate from F-7, F-8, and F-9 was 99.66%, 98.62% and 95.82% and from F-10, F-11 and F-12 was 99.17%, 98.34% and 97.06%. So, it was observed that when formulated with hypromellose 4000 cps, not controlled over 8 hours.

 

Table 2: Release mechanism with variation of n values¹⁴.

n value	Mechanism
n<0.5	Quasi-Fickian diffusion
0.5	Fickian diffusion
0.5<n<1.0	Anomolous (non-Fickian) diffusion
1	non-Fickian case II
n>1.0	non-Fickian super case II

 

Table 3: Properties and percent content of Tablets

Formulation	Diameter (mm) n=10	Thickness (mm) n=10	Hardness (Kp) n=10	Friability(%) n=10	ATS	RTS	Weight variation (mg) n=10	Content (%)
F-1	6.42±0.02	3.22±0.03	3.4±0.02	0.3	0.105	0.105	9.96±0.05	99.77
F-2	6.41±0.01	3.24±0.01	3.3±0.03	0.2	0.102	0.101	9.98±0.05	99.62
F-3	6.43±0.01	3.22±0.02	3.1±0.02	0.2	0.095	0.095	1.01±0.02	99.78
F-4	6.41±0.01	3.21±0.02	3.1±0.02	0.4	0.096	0.096	9.98±0.02	99.81
F-5	6.42±0.02	3.21±0.02	3.3±0.02	0.3	0.102	0.102	9.95±0.05	99.84
F-6	6.42±0.02	3.23±0.01	3.5±0.01	0.3	0.108	0.107	9.96±0.05	99.76
F-7	6.41±0.01	3.24±0.01	3.2±0.02	0.2	0.099	0.098	1.01±0.02	99.73
F-8	6.43±0.01	3.22±0.02	3.2±0.02	0.4	0.099	0.098	9.97±0.05	99.81
F-9	6.43±0.01	3.23±0.02	3.4±0.01	0.3	0.105	0.104	9.99±0.05	99.74
F-10	6.43±0.01	3.24±0.01	3.3±0.03	0.2	0.102	0.101	9.98±0.05	99.77
F-11	6.41±0.01	3.22±0.02	3.1±0.02	0.4	0.096	0.096	1.01±0.02	99.73
F-12	6.42±0.02	3.22±0.03	3.1±0.02	0.3	0.096	0.095	9.96±0.05	99.85
F-13	6.42±0.02	3.24±0.01	3.3±0.02	0.3	0.102	0.101	9.98±0.05	99.83

 

Table 4: Correlation Coefficient, Diffusional Exponenent and MDT of Tablets

Formulation	Correlation Coefficient R2
	Zero order	Higuchi	First order	korsmayer	Diffusional Exponenent (n)	MDT (hour)
F-1	0.9933	0.9936	0.9368	0.9877	0.5664	4.62
F-2	0.9941	0.9918	0.9423	0.9948	0.6005	3.32
F-3	0.9927	0.9933	0.9533	0.9966	0.6669	2.25
F-4	0.9868	0.9963	0.9364	0.9828	0.5199	5.48
F-5	0.9924	0.9804	0.9104	0.9721	0.5812	1.64
F-6	0.9944	0.9766	0.9059	0.9749	0.6324	1.09
F-7	0.9900	0.9961	0.7401	0.9699	0.3621	14.3
F-8	0.9925	0.9935	0.7781	0.9763	0.4459	5.81
F-9	0.9934	0.9918	0.8599	0.9784	0.5268	3.07
F-10	0.9903	0.9932	0.8179	0.9644	0.383	8.44
F-11	0.9978	0.9868	0.8039	0.9595	0.4432	2.19
F-12	0.9969	0.9817	0.8421	0.9702	0.4957	1.24
F-13	0.9852	0.9953	0.7972	0.9822	0.3518	15.73

 

 

After preparing the tablets with carbomer 934P as release rate controlling polymer in F-13, 20% carbomer 934P was used. Six tablets were used in the dissolution study and the release pattern of salbutamol sulphate was monitored up to eight hours. The % of drug release shown in Figure 4. After 1 hour the total percent release from F-13 was 55.29%. And after 6 hours the total percent release from F-13 was 99.21%. It was observed that after 1 hour 50% drug was released i.e. burst release occurred from this.

 

Figure 3: Cumulative percent release vs. time curve of hypromellose 4, 000 cps based matrix tablets

Discussion:

The tablets of different formulations were subjected to various evaluation tests, such as diameter, thickness, uniformity of weight, drug content, hardness, axial and radial tensile strength, friability and in vitro dissolution. All the formulations showed uniform thickness. Good uniformity in drug content was found among all different batches of tablets and the percent drug content was more than 99%. In the present study, the percentage friability for all the formulations was below 1%, indicating that the friability is within the prescribed limits. All the tablet formulations showed acceptable pharmaco-technical properties and complied with the in-house specifications for weight variation, drug content, hardness, and friability.

 

In the formulation of F-1, F-2, and F-3 same polymer (hypromellose 15,000 cps) was used as rate controlling polymer but the ratio was different. In the release profile of these formulas, it can observe that, release is decreases with increasing concentration. And in F-4, F-5 and F-7 ratio of hypromellose 15,000 cps was used same as above but the amount of microcrstalline cellulose and lactose were changed and the release pattern was changed. The graphical presentation of the effect of different polymer at same ratio was shown in the Figure 4.

 

 

In the formulation of F-7, F-8, and F-9 same polymer (hypromellose 4,000 cps) was used but the ratio was different and observed release is decreases with increasing concentration. And in F-10, F-11 and F-12 ratio of hypromellose 4,000 cps was used same as above but the amount of microcrstalline cellulose and lactose were changed. Within 6 hours 99% drug was released.

 

Figure 4: Cumulative percent release vs. time curve of 20% hypromellose 15, 000 cps (F-1), 20% hypromellose 4, 000 cps (F-7) and 20% carbomer 934 p (F-13) based matrix tablets

 

In the formulation F-1, F-7 and F-13, different polymers but same amount was used. In the release profile of these formulations, it can observe that, Hypromellose 15,000 cps has more rate controlling effect than hypromellose 4,000 cps and carbomer 934P.

 

MDT is used to characterize the drug release rate from the dosage form and the retarding efficacy of the polymer. A higher MDT indicates a higher drug-retarding ability of the polymer and vice versa. The MDT value was found to be a function of polymer loading. Table-4 shows that the higher the polymer level, the higher the value of MDT. These findings were in accordance with those of Reza et al. ¹⁷ They investigated the effect of plastic, hydrophilic and hydrophobic types of polymers; their content level; and drugs of different aqueous solubility values on MDT. The studies showed that a direct relationship could be found with MDT value and polymer loading irrespective of drug and polymer type, and that this relationship was linear. The higher MDT value of F-3 indicates a higher drug retaining ability of hypromellose 15000 cps.

 

Comparison with marketed preparations:

The sustained release tablets of salbutamol sulphate were collected from local market and the respective release patterns were observed.  The release profiles shown in Figure 5. In figure 5, the two marketed preparations of sulbutamol SR tablets were compared with the most sustained prepared formulation (F-3). f₂ was calculated to find out the similatiry of the release pattern of F-3 with M-1 and M-2. After calculation, it was observed that F-3 showed f2 value of 39.953 when M-1 was taken as reference standard, whereas F-3 showed f₂ values of  48.230 when M-2 was considered as the reference standard. So, the release pattern of F-3 was found to be more similar with M-2 than M-1.

 

Figure 5: Comparison of F-3 (most sustained release formulation) with the two market preparations.

 

CONCLUSION:

The present study was conducted to evaluate the effect of different viscosity grade polymer on the release profile of Salbutamol Sulphate Sustained release tablets. Sustained release tablets of Salbutamol Sulphate were formulated by direct compression method using Hypromellose 15000 cps, Hypromellose 4000 cps and Carbomer 934P release rate controlling polymer at different concentration. Physical properties such as diameter, thickness, hardness, friability and weight variation of the prepared tablets were evaluated and less variation were observed. Assay of Content uniformity for each formulation were performed and found to be >99% content.  Dissolution studies were carried out with each formulation. Maximum sustaining effect was obtained from F-3 than other formulation which contains Hypromellose 15000 cps (40%) as rate controlling polymer. Different kinetic equations (Zero-order, first-order, Higuchi and Korsmayer’s equation) were applied to interpret the release rate from the tablets. Release profile of Sulbutamol Sulphate from F-1, F-2 F-3, F-7, F-8, F-9 and F-10 showed a tendency to follow Zero order and Higuchi Kinetics. In case of F-5, F-6, F-11 and F-12 showed a tendency to follow Zero order Kinetics. F-4 and F-13 showed a tendency to follow Higuchi Kinetics. Most of formulations follow non-Fickian (anomalous) release except   F-7, F-8, F-10, F-11, and F-13 which showed Fickian (Case І) release.

 

Acknowledgement:

The authors are grateful to Motiar Rahman,GM-QA and Shafi Uddin Ahmed, Asst. Manager, Eskayef Bangladesh Ltd. for the arrangement of ingredients and production facilities.

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Received on 14.10.2009       Modified on 12.12.2009

Accepted on 19.01.2010      © RJPT All right reserved