Microsoft word - final_195__7_.doc

Asian Journal of Pharmaceutical and Clinical Research Research Article

FAST DISINTEGRATING COMBINATION TABLETS OF OMEPRAZOLE AND
DOMPERIDONE
SHAILENDRA KUMAR SINGH*, DINA NATH MISHRA, RISHAB JASSAL, PANKAJ SONI Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology (Accredited as A-Grade by NAAC), Post Box: 38, Hisar (Haryana) 125001, India. ABSTRACT
The aim of this study was to prepare fast disintegrating combination tablets of Omeprazole and Domperidone by
using pertinent disintegrant. The tablets were prepared using mannitol as diluent and sodium saccharin as
sweetening agent along with three different levels of disintegrant. The superdisintegrant used in this study were
Kollidon CL, Ac-Di-Sol and SSG. The tablets were evaluated for weight variation, hardness, friability, wetting
time, water absorption ratio, disintegration time (DT) and dissolution study. Using the same excipients, the
tablets were prepared by direct compression and were evaluated in the similar way. Drug content was estimated
by using HPLC method and also assay of sample was compared with standard drugs (Omeprazole and
Domperidone). Omeprazole and Domperidone were well resolved and the retention times were around 9.01 and
6.2 respectively. From the results obtained, it can be concluded that the tablet formulation prepared with 4.76%
Ac-Di-Sol (internally cross linked form of sodium carboxymethylcellulose) ie. 10 mg showed Disintegration
time of 15 seconds in vitro. Also the hardness, friability, dissolution rate and assay of prepared tablets (batch F7)
were found to be acceptable according to standard limits.

KEYWORDS Omeprazole, Domperidone, Fast disintegrating tablets (FDT’s), Ac-Di-Sol, Direct Compression.

INTRODUCTION
sublimation and wet granulation method3. and elderly have difficulty in swallowing FDTs with sufficient mechanical integrity and to achieve faster disintegration in the oral cavity without water. To achieve this Almost 50% of the population is affected goal, mannitol used as diluent and sodium ineffective therapy.1 Most pharmaceutical Kollidon CL6 in the formulation of tablets. buccal tablets). To obviate the problems were selected for the studies. Omeprazole forms, orally fast disintegrating tablets treatment of ulcers and reflux oseophagitis hardness, dosage uniformity, stability and antiemetic properties) is used for relief on administration, since no water is required nausea and vomiting of any cause, uremia thus suitable for geriatric, pediatric and MATERIAL AND METHODS
traveling patients.2 FDTs can be prepared Materials
compression, freeze-drying, spray drying, Asian Journal of Pharmaceutical and Clinical Research along with their working standard. Sodium into 210-mg tablets using a Hand operated Table 1 - It shows the batches prepared using three different concentration of each
disintegrant
Ingredients
F1 F2 F3 F4 F5 F6 F7 F8 F9
Omeprazole

Domperidone

Mannitol
Kollidon CL
Ac-Di-Sol
Saccharine
Mg. Stearate
Total Wt. of
biconvex. Various batches prepared shown Evaluation of the prepared tablets
Panacea Biotech Ltd., India. Acetonitrile Weight uniformity
were weighed individually and the average chemicals used were of suitable analytical Methodology
Hardness
measured using Monsanto hardness tester. concentrations of the said Friability
superdisintegrants. All the formulations
determined using Roche friabilitor at 25 weight, 3 different superdisintegrants were used in different concentrations ranging Wetting time and water absorption ratio
Asian Journal of Pharmaceutical and Clinical Research Bi Y. et al.8 were used to measure tablet twice was placed in a small culture dish Dissolution studies
(i.d. = 6.5 cm) containing 6 ml of water. A in which two different procedures one for Water absorption ratio, R, was calculated and before water absorption, respectively. 37+0.50C). The samples were withdrawn
at suitable time interval. Samples were
assayed by HPLC

Development of Analytical Procedures
Dissolution of Omeprazole in 0.1 N
HCL.
the gastro resistance of in 0.1 N HCL. The FIG.1 It shows schematization
measurement of tablet wetting time and
Experimental condition
water absorption ratio
Disintegration time (in vitro)
tablets was measured, and the average time and standard deviation were calculated for Dissolution Parameters
each. Three batches for each disintegrant Kollidon CL, SSG, Ac-Di-Sol with varying concentration were prepared and Analysis of Active constituents
HPLC Parameters
of buffer–acetonitrile, and the eluents were Mobile phase: Buffer: Acetonitrile (65:35) was validated statistically for its linearity, mobile phase was a mixture of 0.02 M disodium hydrogen phosphate and Blank Preparation
adjusted to 7.4 by adding orthophosphoric Asian Journal of Pharmaceutical and Clinical Research Standard Preparation
Dissolution parameters
working standard into a dry 200 ml amber colored volumetric flask, add 70 ml of 0.1 ml of this solution was diluted upto 50 ml HPLC parameters
Sample Preparation
Mobile phase: Buffer: Acetonitrile (65:35) placed and operated the apparatus for 120 solution and the liquid was discarded. The Standard Preparation
residue quantitatively into six individual sonicated for 60 minutes. Then 5 ml of the 5 ml of this solution was diluted up to 100 ml with dissolution medium and mixed. Procedure
Sample Preparations
One tablet in each of six bowls was placed and operated the apparatus for 30 minutes. Perform six replicate injections of standard and check for the system suitability test Centrifuged it at 3500 rpm for 15 minutes. criteria. Inject the sample preparation and Procedure
Inject the blank (Dissolution medium) and replicate injections of standard and check Calculation:
for the system suitability test criteria. Dissolution of Domperidone in 0.1N
Calculation
apparatus. The drug content was estimated Experimental condition
Experimental condition
Asian Journal of Pharmaceutical and Clinical Research HPLC parameters
supernatant was diluted up to 50 ml with Mobile phase: Buffer: Acetonitrile (65:35) Procedure
replicate injections of standard and check Standard Preparation
for the system suitability test criteria. quantitatively transfered into the same 100 Calculation
ml volumetric flask. Exactly about 50 ml Linearity Study
blank sample (blank as specified above), Sample Preparation
Transfered the whole content of 10 tablets drug. Solutions of concentration range 2, prepared separately procedure followed is Table 2 - It shows the physical parameters of prepared formulation
Formulations Weight
Hardness
Friability
variation
(Kg/cm2)b
time (sec.)b
absorption
ratio (R)b
Asian Journal of Pharmaceutical and Clinical Research to be in the range of 2-4 kg/cm2. Friability square regression and the intercept, slope mechanical integrity and strength of the determined. The variability of slopes and prepared tablets. Wetting time and water intercepts of the calibration curves were absorption ratio was determined using the determined by constructing the curves. Six method described by Bi et al. (results concentration. The concentrations of the sodium starch glycolate had higher water potency of working standard. The %R.S.D. of the concentration measured within a run wetting of tablets (Table 2). Wetting was (six replicates) was used to determine the closely related to the inner structure of the assay, respectively, and was determined as effect by the mechanism of “swelling”. Ac- RESULTS AND DISCUSSION
disintegrant action by wicking (due to its Physical properties of the formulation
minimum gelling.9,10 Tablet prepared with evaluated for physical parameters such as Ac-di-sol (as in batch F7) had less wetting weight variation, hardness and friability observed between 1.1 and 4.1; well within the acceptable limit for uncoated tablets as disintegration times for formulation F1-F9 per USP. Since mechanical integrity is of was compared (as shown in Table 3), that indicates the formulation (F7) containing Ac-Di-Sol (10 mg) disintegrated the fastest of tablets were determined and were found with no mass left and had good hardness. Table 3 - It shows the Disintegration time (DT) of prepared batches
Disintegrant used
Batch No.
DT (sec.),(n=3)
Comments
per tablet
Asian Journal of Pharmaceutical and Clinical Research Table 4 - It shows the Dissolution results of two different brands and prepared final
formulations (batch F7)
Dissolution
Mean % Drug
of tablets
Concentration
dissolved
found (µg/ml)
Dissolution study
revealed that 94% of was resistant to acid deterioration in 0.1 N HCl after 2 hrs of dissolution. Domperidone release was 99% concentration were analyzed for standard and ten replicates for each prepared tablets and also for different brands (as shown in shown in FIG. 2.b, c respectively. Table 5- Six replicates of each concentration were analyzed for standard and ten
samples for assay.
Injections Analyzed
Concentration
Mean (found)
Standard (µg/ml)
Concentration (µg/ml)
Asian Journal of Pharmaceutical and Clinical Research 0.43µg/ml for Omeprazole and 0.44µg/ml
for Domperidone, which attest the linearity
of the method.
Precision
Domperidone in the precision analysis (n = 6) were 9.35 µg/ml (R.S.D. = 0.35%) and respectively. For R.S.D. values, lower than
2.0%, assure the precision of the method.
Accuracy
addition of Omeprazole and Domperidone reference standards to a mixture of the recovery (n = 6) was 94% and
Domperidone mean recovery was 99%,
demonstrating the accuracy of the method.
Specificity
sample solutions, demonstrating that other FIG. 2. It shows chromatograph
compounds did not co-elute with the main obtained for (a) a sample solution
(combination of Omeprazole and
were well resolved and the retention times Domperidone) (b) dissolution of
Omeprazole (c) dissolution of
Domperidone.
REFERENCES
Validation
Pharmaceutical technology drug delivery, concluded that the tablet formulation (F7) prepared with Ac-Di-Sol (10mg) showed Disintegration time of 15 seconds in vitro. 2. Fini Adamo, Valentina Bergamante , Gian Dissolution data described that the only Carlo Ceschel , Celestino Ronchi ,Carlos Alberto Fonseca de Moraes, Fast dispersible/slow releasing ibuprofen tablets, European journal of pharmaceutics Linearity
3. Brown D., Drug Delivery Technol., 2004, Omeprazole and Domperidone were Y = 14066X (correlation coefficient, r= 4. Weller P. J., Croscarmellose Sodium, 2nd ed., Ainely Wade and Paul, London, 1994, respectively, X: concentration in µg/ml, Y: Omeprazole/ Domperidone peak area ratio. The limit of quantization was 1.44µg/ml Asian Journal of Pharmaceutical and Clinical Research 5. Banker G. S., Sodium Starch Glycolate 2nd edition, Ainely Wade and Paul, London, 1994, 462-466. Development of mouth dissolving tablets of clozapine using two different techniques, Indian journal of pharmaceutical sciences, issue 4, 2008, 526-528 7. British pharmacopoeia 2001 / European K., Otsuka A., Iida K., Preparation and evaluation of compressed tablet rapidly disintegrating in oral cavity. Chem. Pharm. Bull. 44, 1996, 2121-2127. 9. Carter J., The role of disintegrants in pharmaceutical formulation. 2005; In www.pharmainfo.net 10. Yang S., Fu Y., Jeong SH., Park K., J. Pharm. Pharmacol., 56, 2004, 429-436.

Source: http://ajpcr.com/Vol2Issue4/195.pdf