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SIMULTANEOUS ASSAY AND DISSOLUTION PROFILES OF ACECLOFENAC AND PARACETAMOL IN FIXED DOSE COMBINATION TABLETS ON THE KENYAN MARKET By Timina Olive Kayaviri.

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Presentation on theme: "SIMULTANEOUS ASSAY AND DISSOLUTION PROFILES OF ACECLOFENAC AND PARACETAMOL IN FIXED DOSE COMBINATION TABLETS ON THE KENYAN MARKET By Timina Olive Kayaviri."— Presentation transcript:

1 SIMULTANEOUS ASSAY AND DISSOLUTION PROFILES OF ACECLOFENAC AND PARACETAMOL IN FIXED DOSE COMBINATION TABLETS ON THE KENYAN MARKET By Timina Olive Kayaviri U29/3570/2010 Supervisor : Dr. Amugune

2 INTRODUCTION Fixed dose combinations (FDCs)are becoming more popular over the years because they  Are convenient and easy to handle  Confer increased patient compliance.  Reduce development of resistance.  Are cheaper than the individual drugs given concurrently  Have simpler distribution patterns.  Decrease incidences of monotherapy in cases where it’s not recommended.

3 INTRODUCTION…..  Pain is the most common reason patients seek medical attention.  Analgesic therapy that combines individual agents with different mechanisms of action has potential advantages  Example: NSAID- paracetamol combinations such as with aceclofenac.  Combined adverse reactions is a major cause for concern.  Systemic absorption of an orally administered drug in a solid dosage form is a function of disintegration, dissolution and the transfer across membranes.  There is the need for comparative analysis of different brands to assess factors that affect bioavailability

4 JUSTIFICATION  Few post marketing surveillance studies have been done on aceclofenac and paracetamol FDCs  Side effects, widespread use and increasing number of generic products in the market  Brands may contain equal active pharmaceutical ingredient (API) content but have varying dissolution profiles.

5 STUDY OBJECTIVES Overall objective  To determine the quality of different paracetamol and aceclofenac FDCs on the Kenyan market as per the official monographs. Specific objectives  To carry out assay of paracetamol and aceclofenac in FDCs on the Kenyan market.  To carry out dissolution test on these FDCs.  To determine whether the different brands are pharmaceutically interchangable.

6 METHODOLOGY  Eight samples were obtained from different Pharmacies in Nairobi.  Samples contained 100mg aceclofenac and 500mg paracetamol.  Uniformity of weight test was carried out according to the United States Pharmacopoeia (USP).  Assay of the API was carried out using HPLC.  The samples were separated using HPLC system consisting UV – Visible detector at 210nm and a C16 column (15cm x 4.6mm, 5µm), using a mixture of 0.1% v/v triethylamine (pH 3.0) and acetonitrile (50:50) as the mobile phase at a flow rate of 2ml/minute.

7 Methodology…  Dissolution conditions were 900ml dissolution medium (phosphate buffer pH 7.4), medium temperature 37°C  Dissolution tests were carried out using the USP dissolution apparatus II set at 75 revolutions per minute for 45 minutes.  Amount of API dissolved was determined by HPLC under the same conditions as the assay.

8 RESULTS AND DISCUSSION - Uniformity of weight  Tablets had total weights ranging between 650mg and 900 mg.  % relative standard deviation ranged from -4.2 % to 2.6 % compared to the specified range of -5 % to 5 %.  This is the case for all the batches except 004, which had a lower limit of -5.8 %.  Uniformity of weight can be viewed as a measure of the uniformity of content.

9 Uniformity of weight  Variations in weight can be attributed to factors such as  uneven particle sizes and uneven flow of the particles  uneven mixing of the excipients  insufficient amount of lubricant or glidant  the coating film in coated tablets  vibrations  These can be overcome by evaluating particle size before compression, incorporating enough amount of excipients and reducing vibrations.

10 RESULTS AND DISCUSSION - Assay  Run time for the assay was set at twelve minutes and chromatograms obtained, a typical one being shown below.  Peak at 2.58 minutes represents paracetamol while that at minutes represents aceclofenac.

11  The content was calculated by comparing standard and sample peak areas.  % label claim was calculated by comparing the content and the manufacturers label claim.  Manufacturers label claim was that each tablet contains 100mg aceclofenac and 500mg paracetamol.  General USP specifications state that each batch should have API content between 90% and 110% of the label claim.  All the brands complied with the specifications for the assay according to the USP, with values ranging from 95% to 105% for paracetamol and 93% to 104% for aceclofenac except for one (brand 007), whose aceclofenac content was 85%. Assay

12 RESULTS AND DISCUSSION - Dissolution  Chromatograms for the amount of sample dissolved after 45 minutes were obtained after running the sample for twelve minutes.  A typical one is shown below with peak at minutes representing paracetamol and that at minutes representing aceclofenac.

13  The amount of sample dissolved was calculated by comparing standard and sample peak areas.  USP general chapters 711 indicate that every tablet tested for dissolution should be Q+5, where Q is quantity specified in the specific monograph, in this case is considered to be 70%, the lowest % of content dissolved allowed for immediate release tablets.  All the brands tested complied except brand 003 where two tablets complied with the test while four failed to comply and 006 where one tablet had a % dissolution content above 200 %. Dissolution

14 CONCLUSION  Four Brands (001, 002, 005 and 008) complied with all the tests carried out in this study.  50 % of samples complied with all the tests and may be considered to be interchangeable.  The objectives of the study were achieved.  Results are useful in guiding the regulator, clinicians and patients on brands that comply with monograph specifications.  Results may indicate that nearly half of the drugs in the market are not recommended for use.

15 RECOMMENDATIONS  For future studies, the School should facilitate method development and validation for key FDCs.  There is need for more frequent and continuous post marketing surveillance studies on these FDCs.


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