Synthesis, Characterization and Evaluation of Starch Acetate as Rate Controlling Matrix for Controlled Release of Aceclofenac

 

Venkateswara Rao. S1*, Sri Rajini Vege 1, Padmalatha. K2

1Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada–521108, India.

2Department of Pharmacology, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada–521108, India.

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

 

ABSTRACT:

The objective of the present study is to develop Aceclofenac control release matrix tablet formulations by wet granulation method employing starch citrate, a new modified starch. Starch acetate prepared by reacting potato starch with acetic anhydride in the presence of sodium hydroxide at elevated temperatures was insoluble in water and has poor swelling and gelling property when heated in water. The degree of substitution (DS) of starch acetate was found to be 1.60 and high DS develop hydrophobicity are insoluble acetone and chloroform. In the micromeritic evaluation, the angle of repose and compressibility index values revealed the excellent flow characteristic of starch acetate prepared. All the physical properties studied indicated that starch acetate is a promising pharmaceutical excipient in tablets. Aceclofenac, a widely prescribed anti inflammatory analgesic drug belongs to BCS class II and exhibit variable oral bioavailability due to its poor solubility and dissolution rate. Matrix tablets of Aceclofenac (100 mg) prepared employing starch acetate as matrix former in different proportions gave slow and controlled release more than 12 hr. Aceclofenac release was diffusion controlled and dependent on percentage of starch acetate. As the polymer concentration was increased, release rate was decreased. Good linear relationship was observed between percent polymer and release rate (K0). Thus drug release from the matrix tablets could be controlled by varying the proportion of drug: polymer in the matrix.

 

KEYWORDS: Starch acetate, Anti Inflammatory, Matrix tablets, Controlled release and Non-Fickian diffusion.

 

 

INTRODUCTION:

The increasing use of native and modified polysaccharides has resulted in a growing interest in starch as a renewable and environmentally compatible polymer source. However, starch by itself could not be satisfactorily applied in industrial processes. Starch has some disadvantages such as its hydrophilic character, poor mechanical properties, and dimensional stability, especially in an aqueous environment.

 

Chemical modification of starches can enlarge the certain physical properties of the parent starch and enhance their use in a number of applications found in industrial processes and food manufacture. As a result, it is logical to make starch more hydrophobic by replacing the hydroxyl groups (OH) with ester or ether groups. Starch is a natural, biodegradable polymer and modified starches have been used various pharmaceutical purposes such as fillers, superdisintegrants and matrix formers in capsules and tablet formulations. Among the various approaches, preparation of drug matrix tablet is one of the least complicated approach for obtaining controlled release. One of the important modification of starch acetate. Starch acetate is reported to have excellent bond forming ability and suitable for coating and controlled release applications. Much of the literature on starch acetate and its industrial applications are patented, the details of which are not known. In the present work, starch acetate was synthesized, characterized and evaluated as rate controlling matrix former for controlled release. Aceclofenac is a nonsteroidal anti inflammatory (NSAID) drug that reduces pain and inflammation. It has poor aqueous solubility, short biological half life (4 hours) and undergoes  excessive first pass metabolism. So it is prescribed 2-3 times / day, which leads to poor patient compliance. Present studies investigate the possibility for the development of control release tablet of Aceclofenac, to reduce the side effect, dosing frequency and improve patient compliance. Keeping these factors in view it is aim to formulate and evaluate control release Aceclofenac tablets 100 mg, using starch acetate as modified starch polymer.

 

MATERIALS:

Aceclofenac was gift sample from local pharmaceutical company. Potato starch, Acetic anhydride, Lactose, Magnesium stearate, Talc were obtained from Merck Specialities Pvt. Ltd, Mumbai and all other ingredients used were of analytical grade.

 

METHODS:

Synthesis of Starch Acetate:1

Starch acetylation was conducted by a modification of the procedure of Mark and Mehltretter (1972). Potato starch (20 parts), acetic anhydride (80 parts) and sodium hydroxide 50% solution (4.4 parts) were mixed and refluxed for 5 h at 150oC. The reaction mixture was added to cold water to precipitate the starch acetate formed. The product was collected by vacuum filtration, washed repeatedly with water and dried at 80oC for 2 h. The excess cold water was added to terminate the reaction and ground the product before testing.

 

Characterization of Starch Acetate:2

The starch acetate prepared was evaluated for the following properties

 

Solubility:

Solubility of starch acetate was tested in water, aqueous buffers of pH 6.8 and 7.4 and organic solvents such as alcohol, dichloromethane, chloroform and acetone.

 

Identification:

FTIR spectroscopy was used for identification of starch acetate.

 

pH:

The pH of a 1% w/v slurry was measured by using pH meter.

 

 

Melting Point:

Melting point was determined by using melting point apparatus.

 

Viscosity:

Viscosity of 1% dispersion in water was measured using Brookfield viscometer.

 

Swelling Index:

Starch citrate (200 mg) was added to 10 ml of water and light liquid paraffin taken in two different graduated test tubes and mixed. The dispersion in the tubes were allowed to stand for 12 h. The volumes of the sediment in the tubes were recorded. The swelling index of the material was calculated as follows.

 

(Volume of sediment in water) -(Volume of sediment in light liquid paraffin)

--------------------------------------------------------------------X 100

(Volume of sediment in light liquid paraffin)

 

 

Test for Gelling Property:

The gelling property (gelatinization) of the starch and starch citrate prepared was evaluated by heating a 7% w/v dispersion of each in water at 1000C for 30 min.

 

Moisture Absorption:

The hygroscopic nature of starch citrate was evaluated by moisture absorption studies in a closed desiccator at 84% relative humidity and room temperature.

 

Particle Size:3

Particle size analysis was done by optical microscopic method.

 

Density:

Density (g/cc) was determined by liquid displacement method using benzene as liquid.

Bulk Density:4

Bulk density (g/cc) was determined by three tap method in a graduated cylinder.

 

Angle of Repose:

Angle of repose was measured by fixed funnel method.

 

Compressibility Index:5

Compressibility index (CI) was determined by measuring the initial volume (Vo) and final volume (V) after hundred tapings of a sample of starch citrate in a measuring cylinder. CI was calculated using equation

 

Compressibility index (CI) = Vo – V/ Vo X 100

 

 

 

 

Determination of Degree of Substitution:

A powdered starch acetate sample (1.0 g) was placed in a 250 ml flask, and 50 ml of 75% ethanol in distilled water solution were added. The mixture was agitated, warmed to 50oC, held at that temperature for 0.5 h, and cooled and then 40 ml of 0.5 N potassium hydroxide were added. The mixture was then allowed to stand 72 h with occasional swirling. The excess alkali was back titrated with standard 0.5 N hydrochloric acid using phenolphthalein as indicator. A blank was titrated in the same way using an original sample of starch6. The acetylation level was calculated using the equation.

 

Acetylation (%) =

ml (blank) – ml (sample) x Normality of acid x 0.043 x 100/Weight of sample, g (dry basis)

 

The degree of substitution was calculated using the equation –

 

Degree of substitution =

162 x % Acetylation/4300 – (42 x % Acetylation)

 

Where 162 is the molecular weight of the anhydroglucose unit, 42 is the molecular weight of replaceable acetyl group and 4300 is the molecular weight of the acetyl group attached with 100 anhydroglucose unit.

 

Preformulation Studies:

Solubility Analysis:

Pre-formulation solubility analysis was done, which included the selection of suitable solvent system to dissolve the drug as well as various excipients.

 

Melting Point Determination:

Melting point determination of the obtained drug sample was done; as it is a first indication of purity of the sample. The presence of relatively small amount of impurity can be detected by lowering as well as widening in the melting point range.

 

Identification of Pure Drug:

FTIR spectroscopy was used for identification of pure drug.

 

Determination of λmax :

Preparation of Stock Solution:

An accurately weighed 10 mg of Aceclofenac was transferred in a 100ml volumetric flask. To the flask phosphate buffer was added in small proportion so as to dissolve Aceclofenac. The volume was made up to 100ml with phosphate buffer pH 7.4 to get a concentration of 100μg/ml.

 

Determination of λmax:

20μg/ml solution of Aceclofenac was prepared in dilution. The resulting solution was scanned in UV-Vis spectrophotometer from 400- 200nm to determine the λmax.

 

Drug-Excipient Compatibility Studies:

This was confirmed by infrared light absorption scanning spectroscopy (IR) studies. Infra red spectra of pure drug and mixture of formulations were recorded by dispersion of drug and mixture of formulations in suitable solvent (KBr) using Fourier Transform Infrared Spectrophotometer (FTIR).

 

Formulation of Aceclofenac Matrix Tablets:6

Matrix tablets of Aceclofenac (100 mg) were prepared as per the formulae given in the Table 1. The required quantities of medicament, diluent (lactose) and matrix material (starch acetate) were mixed thoroughly in a mortar by following geometric dilution technique. The granulating fluid (solvent blend of water and alcohol in 1:1 ratio) was added and mixed thoroughly to form dough mass. The mass was passed through mesh No.12 to obtain wet granules. The wet granules were dried at 60oC for 4 hours. The dried granules were passed through mesh No. 16 to break the aggregates. The lubricants, talc and magnesium stearate were passed through mesh No. 100 on to dry granules and blended in a closed polyethylene bag. The tablet granules were compressed into tablets on a tablet punching machine (M/s Karnavathi Co. Pvt. Ltd.,) to a hardness of 8 Kg/sq.cm using 8 mm round and convex punches.

 

Table-1: Formulation of Aceclofenac Matrix Tablets

Formulation Code

F1

F2

F3

F4

F5

F6

Ingredients (mg)

Aceclofenac

100

100

100

100

100

100

Lactose

168

162

156

150

138

126

Starch Acetate

5

10

15

20

30

40

Magnesium Stearate

2.5

2.5

2.5

2.5

2.5

2.5

Talc

2.5

2.5

2.5

2.5

2.5

2.5

Total

300

300

300

300

300

300

 

Evaluation of Precompression Parameters:

The flow properties of granules were characterized in terms of angle of repose, carr’s index and hausner’s ratio. The bulk density and tapped density were determined and from this data carr’s index and hausner’s ratio were calculated.

 

Evaluation of Postcompression Parameters:7

The prepared tablets were evaluated for various physicochemical properties like hardness, thickness, uniformity of weight, friability, drug content, disintegration and In-vitro dissolution studies.

 

Hardness:

The hardness of three randomly selected Aceclofenac matrix tablets from each batch was measured by placing each tablet diagonally between the two plungers of tablet hardness tester and applying pressure until the tablet broke down into two parts completely and the reading on the scale was noted down in Kg/cm2. The mean and standard deviation values were calculated and reported.

(Limits: Tablet hardness should be between 4 – 8 kg).

 

Thickness:

Three randomly selected Aceclofenac matrix tablets from batch were used for thickness determination. Thickness of each tablet was measured in mm using Vernier Calipers (Mitutoyo Dial Thickness Gauge, Mitutoyo, Japan). The mean and standard deviation values were calculated and reported.

 

Weight Variation Test:

Twenty tablets were randomly selected from each batch and individually weighed using an electronic balance. The average weight was calculated, individual tablet weight was then compared with the average value to find out the deviation in weight and percent variation of each tablet was calculated.

                      Average weight- Individual weight

% Weight Variation =----------------------------------X 100

                                     Individual weight

 

Friability:

Pre weighed 10 tablets (W0) from each batch were taken in Roche friabilator (Lab India, Mumbai) apparatus that revolves at 100 rpm for 4 minutes dropping the tablets through a distance of 6 inches with each revolution. At the end of test, tablets were re-weighed (W) and the percentage loss was determined. Permitted friability limit is 1%. The % friability was then calculated by –

 

% F = 100 (1-W0/W)

Drug Content Estimation:

Ten randomly selected tablets from each formulation (F1 to F6) were finely powdered and powder equivalent to 100 mg of Aceclofenac was accurately weighed and transferred to 100 ml volumetric flasks containing 50 ml of phosphate buffer (pH 7.4). The flasks were shaken thoroughly to get uniform solution/suspension. The volume was made up to the mark with the above phosphate buffer and filtered. One ml of the filtrate after suitable dilution was subjected for the estimation Aceclofenac content at 275 nm using a double beam UV-visible spectrophotometer. Each reading was carried out in triplicate and the average Aceclofenac content in the matrix tablet was calculated.

 

Disintegration Time:

Disintegration time was determined in a Thermonic tablet disintegration test machine using water, 0.1N HCl and phosphate buffer of pH 7.4 as test fluids.

 

In vitro Drug Release Study:8

The In-vitro dissolution study was conducted as per the United States Pharmacopoeia (USP) XXIV. The rotating paddle method was used to study the drug release from the tablets. The dissolution medium consisted of 900 ml of phosphate buffer (pH 7.4). The release was performed at 370C ± 0.50C, at a rotational speed of 50 rpm. Five ml samples were withdrawn at predetermined time intervals over the period of 24 hr and the volume was replaced with fresh medium. The samples were filtered through Whatman filter paper and analyzed for Aceclofenac after appropriate dilution by UV spectrophotometer at 275 nm. The percent drug release was calculated using the calibration curve of the drug in phosphate buffer pH 7.4.

 

Drug Release Rate:

The release rate of Aceclofenac from matrix tablets was determined by using zero order equation.

 

Qt – Qo = Ko t

 

Where, Qo = Initial amount of drug

Qt = Amount of drug at time t

Ko = Zero order rate constant

 

RESULTS AND DISCUSSION:

Synthesis of Starch Acetate:

Acetylation of potato starch to high degree of substitution (DS) was studied by reacting starch with acetic anhydride using 50% aqueous NaoH as the catalyst. During acetylation, three free hydroxyl groups on C2, C3, and C6 of the starch molecule can be substituted with acetyl groups. The expected chemical reactions are illustrated in Fig. 1. Reaction 1 is the main rate-controlled reaction involving a base catalyst, where starch is acetylated with acetic anhydride and a base catalyst. The primary OH on C6 is more reactive and is acetylated more readily than the secondary ones on C2 and C3 due to steric hindrance. The primary OH located at the exterior surface of the starch molecules reacts readily with the acetic groups, while the two secondary ones located within the interior surface of starch form hydrogen bonds with the OH groups on the neigh- boring glucose unit. The OH on C2 is more reactive than the one on C3, mainly because the former is closer to the hemi-acetal and more acidic than the later. Side reactions 2 and 3 rarely occur because almost no water exists in this reaction system.

 

 

Fig-1: Chemical Reaction in synthesis of Starch Acetate

 

 

Characterization of Starch Acetate:

The starch acetate prepared was characterised by determining various physicochemical properties. The properties of starch acetate are summarised in Table 2. Starch acetate prepared was found to be white, crystalline, non hygroscopic powder and can easily be ground to different sizes. This powder has an average particle size of 5.58 μm. The starch acetate prepared was insoluble in water, aqueous buffers of pH 1.2 and 7.4, methanol, petroleum ether, dichloromethane, cyclohexane and chloroform. When tested for melting point, it was charred at 2600C. In water it exhibited good swelling index (3.5%). No gelling/pasting was observed with starch acetate when its aqueous dispersion was heated at 1000C for 30 min, where as potato starch formed a paste/gel during the above heat treatment. In the micromeritic evaluation, the angle of repose and compressibility index values revealed the excellent flow characteristic of starch acetate prepared. The percent acetylation was 30.1 % and the degree of substitution was found to be 1.606. All the physical properties studied indicated that starch citrate is a promising pharmaceutical excipient in tablets.

 

Table-2: Physicochemical Properties of Starch Acetate

PROPERTIY

RESULTS

Solubility

Insoluble in all aqueous and organic solvents tested

pH of a 1% w/v

5.8

Melting Point

260OC

Viscosity of 1% w/v

2.4 cps

Swelling Index

466.6

Test for gelling property

No gelling and the swollen particles of starch acetate separated from water. Whereas in the case of potato starch, it was gelatinized and formed gel.

Moisture absorption

3.5 %

Particle size

5.58 μm

Density

0.812 gm/cc

Bulk density

0.967 gm/cc

Angle of repose

18.36

Compressibility index

16.02

Degree of Substitution

1.606

 

 

 

 

Identification of Starch Acetate:

The IR spectrum (Fig. 2) of starch acetate showed the acetyl carobonyl stretching at 1731.27 cm-1, which was absent in the IR spectrum (Fig. 3) of potato starch, indicating the acetylation of the native starch.

 

Fig-2: IR Spectra of Starch Acetate

Fig-3: IR Spectra of Potato Starch

 

 

Preformulation Studies:

Identification of Pure Drug:

FT-IR spectroscopy was used to determine the functional group present in the pure drug sample. The spectrum of Aceclofenac are shown characteristic bands at 3319.13 cm-1 (N-H stretching), 2971. 17 and 2103.85 cm-1 (O-H stretching), 1717.24 cm-1 (C-O stretching), 1589.71 cm- 1(skeleton vibration of aromatic C-C stretching for NH) 1345.02 cm-1 (O-H in plane bending), 1281.48 cm-1 (CN aromatic amine), 943.36 cm-1(O-H out plane bending) and 749.16 cm-1 (out plane bending for N-H). IR Spectra of Aceclofenac as follows:

 

Fig-4: IR Spectra of Pure Drug Aceclofenac

 

Fig-5: UV Spectra of Aceclofenac

 

Solubility Studies:

Solubility of Aceclofenac was determined in different media including distilled water, 0.1 N HCL and Phosphate buffer pH 7.4. Excess amount of Aceclofenac was added into three different conical flask containing 100 ml of distilled water, 0 .1 N HCL and phosphate buffer pH 7.4. These solutions were shaken for 48 h at room temp on a magnetic stirrer. After equilibrium, the suspensions were filtered through 0.45 μm Millipore membrane filters. The filtrate was appropriately diluted and the concentration of the Aceclofenac in the filtrate was determined by UV spectrophotometer Labindia- 3000, Japan at 275 nm. Solubility of Aceclofenac in water, 0.1 N HCL and Phosphate buffer pH 7.4 were found to be 88.6, 33.6 and 1058.9 μg/ml.

 

Melting Point Determination:

After performing capillary method melting point of Aceclofenac found in range of 152-153oC.

 

Determination of λmax:

The Aceclofenac solution was scanned in UV-Vis spectrophotometer from 400- 200nm to determine the λmax. The λmax was found to be at 275 nm, so the calibration curve of Aceclofenac was developed at this wavelength.

 

Drug Excipients Compatibility Studies:

The compatibility studies were carried out to ascertain any kind of interaction of drug with the excipients used in the preparation of tablets.

 

Fig-6: IR Spectra of Pure Drug Aceclofenac

Fig-7: IR Spectra of Aceclofenac and Formulation mixture

 

Inference:

The IR spectral analysis of Aceclofenac and the physical mixture of Aceclofenac and starch acetate are presented in Figure7 respectively. Pure Aceclofenac spectra showed principal peaks at different wave numbers corresponding to its functional groups, confirming the purity of the drug as per established standards. All the above characteristic peaks appear in the spectra of physical mixture of Aceclofenac and starch acetate, indicating no modification or interaction between the drug and starch acetate.

 

Formulation of Aceclofenac Matrix Tablets:

Matrix tablets of Aceclofenac could be prepared by employing different proportions of starch acetate by conventional wet granulation method. Starch acetate was added at 2, 4, 6, 8, 12 and 16 % in tablet weight and assess it influence on drug release characteristics. A total of six (F1 – F6) formulations were prepared using Aceclofenac as potent drug and starch acetate as release retardant polymer. The diluent lactose was also incorporated in the tablets. Magnesium stearate and talc were added in a final step and mixed, The Blend was compressed on 8 mm biconcave multiple punch tablet compression machine. Each tablet weighing 300 mg corresponding to 100 mg of Aceclofenac were obtained.

 

Evaluation of Precompression Parameters:

Before compression the tablet blend was subjected to analysis of precompression parameters which included Bulk density, Tap density, Carr’s index, Hausner’s ratio and Angle of repose and the values were reported in Table 3. The angle of repose of the different batches of powders was determined as per method mentioned earlier and the results ranged between 17.74 -25.17. The powder with angle of repose less than 250 indicates good flow properties. The bulk density was found in the range of 0.73±0.29- 0.84±0.14gm/cm3. The tapped density ranged between 0.76±0.32 - 0.87±0.26gm/cm3. The percentage compressibility an indirect method of measuring powder flow ability developed by carr’s, was calculated and it is good agreement with the results of angle of repose and hausner’s factor. All these results indicates that the powder possesses excellent flow properties and compressibility.

 

 

Table No -3: Evaluation Precompression parameters

Formulation Code

Bulk density (gm/cm3)

Tapped density (gm/cm3)

Carr’s index

Hausner’s ratio

Angle of repose (%)

F1

0.76±0.27

0.83±0.31

8.43±0.65

1.09±0.02

17.74±0.14

F2

0.73±0.29

0.77±0.25

5.19±0.65

1.05±0.03

24.22±0.26

F3

0.84±0.14

0.87±0.26

5.44±0.66

1.03±0.24

25.17±0.23

F4

0.83±0.17

0.86±0.18

3.48±0.58

1.03±0.26

25.56±0.25

F5

0.76±0.14

0.78±0.28

3.46±0.55

1.02±0.13

24.70.±0.42

F6

0.74±0.36

0.76±0.32

3.63±0.27

1.02±0.16

24.22±0.18

Mean ± S.D. of three determinations

 

Evaluation of Postcompression Parameters:

All the formulations were prepared under similar conditions and the tablets exhibited white color, convex in shape with smooth surface. The data obtained for post compression parameters such as hardness, friability, weight variation, uniformity of content, thickness, are shown in Table No -4. The hardness for the tablets of all formulations was adjusted to 6.8–8.0 Kg/cm2 so that indicating good mechanical strength with an ability to withstand physical and mechanical stress conditions while handling. The thickness was measured for the tablets of all formulations and was found to be within the acceptable range. The weight of the tablet varied between 297 ± 0.28 to 303 ± 0.58 mg for all the formulations. All the tablets passed weight variation test as the ±5% weight variation was within the pharmacopoeial limits. In all the formulations, the friability value is less than 1% and meets the IP (Indian Pharmacopoeia) limits;indicate good mechanical resistance of the tablet. The drug content varied between 99.54%±0.5 to 101.31%±0.2 for all the formulations. The content of all the tablets was found to be uniform with low standard deviation values indicating efficient mixing of drug, polymer and excipients.

 

Table No -4: Evaluation Parameters of Aceclofenac matrix tablets

Formulation Code

Hardness (Kg/cm2)

Friability (%)

Weight Variation (mg)

Thickness (mm)

Drug Content (%)

F1

6.9±0.22

0.29±0.12

299±0.65

4.92±0.55

99.61±0.45

F2

6.8±0.55

0.42±0.25

300±0.55

4.73±0.24

101.31±0.25

F3

7.4±0.51

0.51±0.58

301±0.58

4.83±0.32

99.54±0.55

F4

7.8± 0.25

0.58±0.36

297±0.69

4.9±0.33

99.79±0.58

F5

8.1±0.69

0.52±0.64

300±0.45

4.96±0.85

99.82±0.54

F6

6.8± 0.25

0.53±0.58

303±0.28

4.83±0.55

99.69±0.58

Mean ± S.D. of three determinations

 

 

 

Table -5: Cumulative % drug release from Aceclofenac matrix tablets

Time (hr)

F1

F2

F3

F4

F5

F-6

0

0

0

0

0

0

0

1

38.91

34.92

32.24

27.65

21.36

17.25

2

56.24

48.92

46.42

44.21

38.12

30.56

4

62.84

59.21

58.91

55.83

49.53

41.32

6

86.78

74.93

67.24

64.26

58.44

50.21

8

100

89.72

78.84

73.87

66.83

56.29

10

---

100

88.78

86.38

76.47

63.21

12

---

---

100

93.71

82.74

68.38

 

 

Evaluation of In Vitro Release Studies:

The in vitro drug release studies were performed to evaluate the release of Aceclofenac from matrix tablets. The drug release of six formulations was compared with each other and the results are represented diagrammatically in Fig-8. The percentage drug release from F1, F2 and F3 formulations was found to be 100% after 8, 10 and 12 hours time intervals. The percentage drug release from F4, F5 and F6 formulations was found to be 93.71, 82.74 and 68.38 after 12 hours time intervals. From all the formulations F6 formulation shows slow drug release when compared to other five formulations. The result indicates that the percentage of starch acetate increase the drug release was decrease and the formulation F6 contains highest concentration of 16% starch acetate.

 

 

Fig-8: Cumulative % drug release from Aceclofenac matrix tablets

 

 

Release Rate of Aceclofenac Matrix Tablets:

The release rate of Aceclofenac from matrix tablets was determined by using zero order equation. The graph was plotted between percentage polymer verses release rate and it given steep down curve.

 

 

 

Table -6: Relationship between percent polymer and release rate (K0)

Percent polymer

Release rate (k0)

2

12.5

4

10.0

6

8.30

8

7.80

12

6.80

16

5.30

 

 

Fig -9: Relationship between percent polymer and release rate (K0)

 

 

As the polymer concentration was increased, release rate was decreased. Good linear relationship was observed (Fig. 9) between percent polymer and release rate (K0). Thus drug release from the matrix tablets could be controlled by varying the proportion of drug: polymer in the matrix.

 

CONCLUSION:

Starch acetate prepared by reacting potato starch with acetic anhydride at elevated temperatures was insoluble in water and has no pasting or gelling property when heated in water. In the micromeritic evaluation, the angle of repose and compressibility index values revealed the excellent flow characteristic of starch acetate prepared. All the physical properties studied indicated that starch citrate is a promising pharmaceutical excipient in tablets. Aceclofenac release from the tablets formulated employing starch acetate was slow and controlled more than 12 hr and depended on percentage of polymer in the tablet. Aceclofenac release from F6 formulation employed 16 % starch acetate was showed better controlled release than other formulations. Hence the starch acetate polymer is suitable for the design of oral controlled release of Aceclofenac.

 

ACKNOWLEDGMENT:

The presenting authors are thankful to Vijaya institute of pharmaceutical sciences for women, Vijayawada for their valuable support in carrying out this work.

 

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5.     Cooper J and Gunn C. Tutorial Pharmacy 1986; 211-233.

6.     Chowdary KPR, Veeraiah Enturi and Sravani P; Formulation Development of Etoricoxib Tablets by Wet Granulation and Direct Compression Methods Employing Starch Citrate; RJPBS; 2011; 9(1): 983-993.

7.     L. Lachman, A. Liberman, J. L. Kanig. The theory and practice of industrial Pharmacy, 4th edition, Varghese publishing house, Bombay.1991, pp.67-68.

8.     Chowdary KPR & Tripura Sundari P; Evaluation of Calcium Starch : A New Starch Based Polymer for Controlled Release of Diclofenac; Int. J. Chem. Sci.: 6(3), 2008, 1189-1195

 

 

 

 

Received on 17.08.2016          Modified on 14.09.2016

Accepted on 13.10.2016        © RJPT All right reserved

Research J. Pharm. and Tech. 2017; 10(1): 121-130.

DOI: 10.5958/0974-360X.2017.00028.2