Vol - 4, Issue - 3, Supl - 1 Apr-Jul 2013 ISSN: 0976-7908 Parekh et al www.pharmasm.com IC Value – 4.01 228 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES FORMULATION DEVELOPMENT AND EVALUATION OF ORAL IN-SITU FLOATING GEL OF DOMPERIDONE K. S. Parekh* and K. V. Shah School of Pharmacy, RK University, Kasturbadham, Rajkot, Gujarat, India. ABSTRACT Oral tablet administration to patients is a significant problem and has become the object of public attention. The demand for liquid dosage forms that can be easily ingested is particularly strong in the pediatrics and geriatric markets. Domperidone is a weakly basic drug used for treatment of upper gastrointestinal motility disorders such as nausea and vomiting. It is a weak base, which when exposed to environments of increasing pH results in precipitation of poorly soluble free base within the formulation. To resolve this problem the oral in-situ floating gel of Domperidone was formulated. The formulations of sodium alginate (F1-F6), poloxamer 407 (F7-F13) and combination of both the gelling polymers (F13-F16) along with HPMC K100 M as release retardant, were prepared and evaluated. CaCO 3 is added which provided Ca 2+ ion for gelation and CO 2 which gets entrapped in gel matrix and induced floating of gel. The In-vitro drug release profile of all formulations was determined. Formulations F13-F16 provided sustained release for more than 9 hours. F14 showed 89.69% drug release over the period of 11 hours. Viscosity of all formulations was in acceptable range. The use of Poloxamer 407 and HPMC K 100M along with sodium alginate prolonged the release of drug from gel matrix. Keywords: Domperidone, Sodium alginate, Poloxamer 407, HPMC K100 M, Floating gel. INTRODUCTION Many patients have difficulty in swallowing tablets and capsules and consequently do not take medications as prescribed. It is estimated that 50% of the population is affected by this problem, which results in a high incidence of noncompliance and ineffective therapy. Because the changes in various physiological functions associated with aging including difficulty in swallowing, current dosage forms, like tablets and capsules, are impractical. [1] The demand for liquid dosage forms that can be easily ingested is particularly strong in the pediatrics and geriatric markets, with further application to other patients who prefer the convenience of a readily administered dosage form. [1] Oral sustained release dosage forms (SRDFs) have been developed for the past three decades due to their considerable therapeutic advantages. However, this approach has not
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Vol - 4, Issue - 3, Supl - 1 Apr-Jul 2013 ISSN: 0976-7908 Parekh et al
www.pharmasm.com IC Value – 4.01 228
PHARMA SCIENCE MONITOR
AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES
FORMULATION DEVELOPMENT AND EVALUATION OF ORAL IN-SITU
FLOATING GEL OF DOMPERIDONE
K. S. Parekh* and K. V. Shah
School of Pharmacy, RK University, Kasturbadham, Rajkot, Gujarat, India.
ABSTRACT Oral tablet administration to patients is a significant problem and has become the object of public attention. The demand for liquid dosage forms that can be easily ingested is particularly strong in the pediatrics and geriatric markets. Domperidone is a weakly basic drug used for treatment of upper gastrointestinal motility disorders such as nausea and vomiting. It is a weak base, which when exposed to environments of increasing pH results in precipitation of poorly soluble free base within the formulation. To resolve this problem the oral in-situ floating gel of Domperidone was formulated. The formulations of sodium alginate (F1-F6), poloxamer 407 (F7-F13) and combination of both the gelling polymers (F13-F16) along with HPMC K100 M as release retardant, were prepared and evaluated. CaCO3 is added which provided Ca2+ ion for gelation and CO2 which gets entrapped in gel matrix and induced floating of gel. The In-vitro drug release profile of all formulations was determined. Formulations F13-F16 provided sustained release for more than 9 hours. F14 showed 89.69% drug release over the period of 11 hours. Viscosity of all formulations was in acceptable range. The use of Poloxamer 407 and HPMC K 100M along with sodium alginate prolonged the release of drug from gel matrix.
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Figure 4: Cumulative % drug release (F1-F6)
Figure 5: Cumulative % drug release (F8, F9, F11, F12)
Figure 6: Cumulative % drug release (F13, F14, F15, F16)
In-vitro dissolution studies showed that formulation F14 showed 89.69% drug release
over the period of 11 hours. More over it was also depicted that increased concentration
Time
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of HPMC K 100 M was useful for sustained drug delivery. Use of Poloxamer 407 also
added to decrease the drug release and prolonged the drug release.
The results obtained from in vitro release studies of the optimised batch (F14) was
attempted to fit into various mathematical models. The regression coefficient (r2) values
of zero order, first order, Higuchi matrix, Peppas and Hixson-Crowell are tabulated in
table-7 for optimised formulation. From the table, it is clear that the drug is released in a
controlled manner over a period of time and shows zero order drug release for all
formulations.
TABLE 7: IN-VITRO DRUG RELEASE PROFILE OF DOMPERIDONE
FORMULATION F14
Formulation R2 value
Best fit model Higuchi
Zero order
First order
Hixon-crowell
K Peppas
F14 0.967 0.996 0.962 0.982 0.969 Zero order
Figure 7: In-Vitro Drug release profile of Domperidone Formulation F14 (Zero
Order)
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Figure 8: In-Vitro Drug release profile of Domperidone Formulation F14 (First
Order)
Figure 9: In-Vitro Drug release profile of Domperidone Formulation F14 (Higuchi
Matrix)
Figure 10: In-Vitro Drug release profile of Domperidone Formulation F14 (Hixon-
crowell)
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Figure 11: In-Vitro Drug release profile of Domperidone Formulation F14 (K
Peppas Treatment)
10. Measurement of Drug Content
The absorbance of the suitably diluted solutions was measured. All the readings were
measured in triplicate and the average of the % Drug content is determined by using
standard calibration curve taken at 284 nm. (Table - 8)
TABLE 8: MEASUREMENT OF DRUG CONTENT OF IN-SITU GELLING
SOLUTIONS
Formulations Average% drug content
1 102.89
2 102.63
3 98.65
4 101.03
5 101.44
6 99.17
7 100.20
8 102.17
9 100.10
10 100.51
11 101.39
12 100.98
13 101.13
14 99.22
15 101.29
16 102.22
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In the present study the content uniformity of all the batches are found to be in the range
of 98.65-102.89. Hence all the batches have passed the content uniformity test, because
all the batches lies within the acceptable limit.
11. Stability Study
11.1 In-Vitro Drug Release Studies
Figure 12: Stability Study of Optimized Formulation at Room Temperature
Stability study was carried out for optimized formulation at room temperature for 1
month. The cumulative drug release of optimized formulation F14 showed that 89.69%
drug got released in 11 hours, while after one month the percent drug release was found
to be 92.96% in 11 hours. So, there was no major change during one month.
11.2 Measurement of viscosity, pH and % drug content
TABLE 9: MEASUREMENT OF GENERAL PARAMETERS OF OPTIMISED
FORMULATION AFTER 1 MONTH
Formulation F14 pH Viscosity of solution and gel (cp)
% drug content
Before one month 8.53 290.33 2166.67 99.22 After one month 8.46 309.6 2119.33 100.97 No significant difference in the pH, viscosity and % drug content was found during the
period of 1 month.
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