II. Quantitative drug analysis and evaluation of the
influence of accelerated stability testing on the in vitro dissolution.
Immediate release solid dosage forms are routinely subjected
to tests such as content uniformity, weight, friability, hardness and
disintegration, tests mainly performed by manufacturers to assess
batch-to-batch uniformity. As the efficacy and safety of a dosage form is
dependent on the content of active ingredient, the test for drug content is
recommended in pharmacopoeia monographs. The test which is often most
associated with the assessment of in vivo performance is the in vitro
dissolution test, because even when a formulation contains the right amount of
drug it can fail to release the content at the site of absorption due to the
poor dissolution.
- Dissolution tests are used to assess the dissolution
properties of the drug itself in order to choose appropriate excipients for the
formulation.
- Dissolution tests are a very important tool to ensure
continuing product quality and performance after certain changes, such as
changes in the formulation, the manufacturing process, the site of manufacture,
and the scale-up of the manufacturing process (Guidance for industry, 1997).
- Clinical scientists rely on dissolution tests to establish
an in vitro/in vivo correlation between drug release from the dosage form and
drug absorption. The dissolution of an oral solid product can impact the rate
and the amount of drug available for absorption and hence influence the
therapeutic efficacy of the product. It is essential that the dissolution
characteristics remain unchanged throughout the product shelf life.
- Generally in developing countries, where technology and other
resources are limited to conduct an in vivo bioequivalence study, appropriate
dissolution studies, such as profile comparison between the local generic
product and the reference product under different test conditions may be used
to assure product quality (Shah, 1998).
Stability of a pharmaceutical product means the maintenance of
the quality defined in the specifications of the drug product up till the end
of the manufacturer's stated shelf life. The quality of the drug product is
determined by the content and purity of the active ingredient and by the
organoleptic, physiochemical and microbiological properties (Grimm, 1986).
Stability tests are a series of tests designed to obtain
information on the stability of pharmaceutical products, in order to define
their shelf life and utilisation period under specified packaging and storage.
Dissolution stability is an important tool to assess the quality of the
product. Is therefore both the legal and ethical responsibility of the
manufacturer to ensure that the product meets all the quality specifications
during the shelf life period as long as it is stored under the conditions
specified on the label.
For worldwide stability tests, the earth is divided into four
climatic zones into which individual countries are assigned. Rwanda can be
assigned to the climatic zone II (subtropical and Mediterranean climates,
storage conditions 25°C/60% RH) (Grimm, 1998). If imported drug
formulations have not been optimised for the corresponding climate zone, their
effectiveness may be compromised during transportation or/and storage.
Regarding the regulatory aspects, the WHO recommends an
accelerated stability test under zone IV climatic conditions (storage
conditions of 40 °C / 75 % RH) to be performed on all drugs intended for
the global market (Matthews, 1999).
II.1. Amoxicillin formulations
II.1.1 Material and equipment
Materials
· Amoxyphar 250 mg capsules ( Labophar,
Rwanda)
· Elymox 250 mg capsules (Elys chemical
industries, Kenya)
· Amoxysha 500 mg capsules (Dilam, Canada)
· Amoxicillin (Alpha Pharma, Belgium)
· Acetonitrile (Biosolve, The Netherlands)
· Monobasic potassium phosphate (Vel, Belgium)
All these chemicals and reagents were at least of analytical
grade.
Equipment
· Incubator: U-60 (Memmert, Analis, Namen,
Belgium)
· Column: Lichrospher 100 RP-C 18 e (5um), 250X4
mm
(Merck-Hitachi, Darmstadt,
Germany)
· Detector: L-7400 UV detector (Merck-Hitachi,
Darmstadt, Germany)
· Pump: L-7100 pump (Merck-Hitachi,
Darmstadt, Germany)
· Integrator: D-7000 integrator (Merck-Hitachi,
Darmstadt, Germany)
· Software Package `HPLC System Manager'
(Merck-Hitachi, Darmstadt,
Germany)
· Lambda 12 UV/VIS Spectrophotometer
(Perkin Elmer UV/VIS,
Perkin Elmer, Norwalk, USA)
· Dissolution equipment (VK 7000, Vankel
Technology, Cary, NC, USA)
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