You are hereFORMULATION AND EVALUATION OF AMOXICILLIN TRIHYDRATE MODIFIED RELEASE DOSAGE FORMS

FORMULATION AND EVALUATION OF AMOXICILLIN TRIHYDRATE MODIFIED RELEASE DOSAGE FORMS



Figure 5.4:FT-IR spectrum of physical mixture of amoxicillin trihydrate and ethyl cellulose


Figure 5.5: FT-IR spectrum of physical mixture of amoxicillin trihydrate and HPMC K4M


Figure 5.6: FT-IR spectrum of physical mixture of amoxicillin trihydrate and METHOCEL

FORMULATION DEVELOPMENT
Theoretical Drug Release Profile

The theoretical drug release profile calculation is important to evaluate the formulation with respect to release rates and to ascertain whether it releases the drug in a predetermined manner.Theoretically drug release profile was calculated by using the pharmacokinetic data. Attempts were made to develop formulations using available polymers, the combination of which shows dissolution profile that matches with the theoretical drug release profile.

Dose calculations: The total dose of amoxicillin for once daily modified release formulation was calculated by the following equation using the available pharmacokinetic data.26, 27, 28

F = bioavailability =85 to 90%
Css = steady state concentration = 2 µg/ml
Vd = volume of distribution = 0.3 l/kg = 18000ml per 60 kg.
T1/2 = half life = 1.02 hr
ClT = total clearance
XL = loading dose
DM = maintenance dose
DT = total dose = XL + DM

XL = Css* Vd
       ---------- 
           F

= 2* 18000 / 0.9

= 40,000 µg = 40 mg

ClT = 0.693 Vd / T1/2 = 13860 ml/hr

DM = Css * ClT* Time
        ------------------
                  F   

= 2 * 13860 *24 / 0.9 = 739.2 mg

DT = XL + DM = 40+739.2 = 779.2 mg

According to theoretical release pattern, once daily amoxicillin modified release formulation should release 40 mg in 1 hour, 30.8 mg every hour, and 100% in 24 hours.

Table 5.4: Dissolution profile of amoxicillin trihydrate according to theoretical calculations

Sampling time (hr)

% drug release

1

9.08

2

13.03

4

20.94

6

28.85

8

36.75

10

44.66

12

52.56

16

68.37

20

84.18

24

100


Figure 5.7:Dissolution profile of amoxicillin trihydrate according to theoretical calculation

TABLET
Development of the formulation in the present study was mainly based on the type of polymer, concentration of polymers, and the drug. Various polymers and excipients in different combinations were used so as to get tablet with good physical properties and in vitro drug release from tablet. Amoxicillin trihydrate is water soluble drug, and dose taken is 775 mg. So, in the present study attempts were made to get good physical and release profile of the tablets.

Manufacture of Tablets
As described in the methodology chapter the tablets were prepared by different method. In this method, all the excipients and drug were geometrically mixed and that blend was used for compression. Different polymers were used in different concentrations to get good release of drug.  Different excipients like delayed release polymer, coating material, lubricants were used to get the tablets with acceptable physical properties.

Tablet prepared by using coating material and HPMC K4M:
The tablets were manufactured for the batches T1 to T3 using the ingredients shown in the Table 4.10.  After getting all physical properties of the granule satisfactory, tablets were prepared. Physical as well as drug release pattern were studied for each batch. Physical properties of the granules are shown in theTable 5.5.The properties of the manufactured tablets areshown in theTable 5.6.

Table 5.5:Physical properties of the granules of the batches T1 to T3

Parameter

T1

T2

T3

angle of repose(0)

36.02

36.52

33.6

Bulk density(gm/ml)

0.566

0.543

0.50

Tapped density(gm/ml)

0.610

0.636

0.58

Haussner’s Ratio

1.07

0.85

1.16

Compressibility Index (%)

7.21

14.62

13.79

Table 5.6: Properties of the tablets for the batches T1 to T3

Parameter

T1

T2

T3

Hardness (kg/cm2)(n=6)

9.5 +0.9

9 + 0.2

12 + 0.5

Friability (%)

0.0032

0.003

0.001

Uniformity of weight (gm)

1.0687 +5%

1.212 + 5%

1.300 + 5%

Drug content (%) (n=3)

97.5+ 0.02

97.17+0.06

98.1+0.20

Thickness (mm)(n=6)

6.79 +0.008

7.74 + 0.01

8.30 +0.02

Dissolution profile of the tablets for the batches T1 to T3:
After getting all the physical parameters satisfactory for batches T1 to T3, the dissolution of these batches was tested. Dissolution was carried out as per the procedure mentioned in methodology chapter. The details of the dissolution study for the tablets of the batches T1 to T3are given in the Table 5.7 and in Figure 5.8.

Table 5.7: In vitro release of Amoxicillin trihydrate from tablets of batch T1 to T3

Time (hours)

Cumulative percentage of drug released (%)

T1 (n=6)

T2 (n=6)

T3 (n=6)

1

74.79+ 0.1

7.28+ 0.02

71.64+ 0.42

2

79.79+ 0.1

11.95+ 0.1

85.21+ 0.63

4

97.62+ 0.07

24.90+ 0.05

98.10+ 0.37

6

-

30.34+ 0.1

-

8

-

34.77 + 0.2

-

10

-

55.81+ 0.08

-

12

-

62.63+ 0.3

-

16

-

82.39+ 0.36

-

20

-

98.03+ 0.2

-

24

-

-

-


Figure 5.8:Comparison of in vitro release of Amoxicillin trihydrate from the tablets of the batches T1 to T3 with theoretical drug release profile.

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