| Drugs subjected to hydrolysis: | *water reduced or eliminated from the system. |
| *water-labile drugs | waterproof protective coating applied in the tablet or
tightly closed containers must be used |
| Drugs subjected to hydrolysis: | *water reduced or eliminated from the system. |
| *in liquid formulation | water replaced by substitute liquids such as
alcohol, Propylene glycol and glycerin. |
| *for injectable products | anhydrous vegetable oils may be used as
solvent |
| For unstable antibiotic drugs | supplied in
dry form for reconstitution before dispensing |
| For unstable preparations: | storage under refrigeration |
| 1 major determinant in stability
2 optimum stability in pH
3 __ agents increases stability | 1 pH
2 pH 5 & 6
3 buffering |
| Oxygen sensitive drugs | prepared in dry state
*packaged in sealed containers with air replaced by inert gas (Nitrogen, carbon dioxide).
*add antioxidants |
| 1 Oxygen sensitive drugs adding antioxidants in Aqueous preparations
2 Oxygen sensitive drugs adding antioxidants in oleaginous/unctuous preparations | 1 Na2SO3, NaHSO3, H3PO2, ascorbic acid
2 alpha tocopherol, butylhydroxyanisole
& ascorbyl parmitate |
| It is the source of difficulty in preparing stable solutions of oxidizable drugs | trace metals in drug, solvent, container or stopper |
| trace metals in drug are eliminated by: | 1 purification of source of contaminant
2 complexing or binding metal by using specialized agents
(chelating agents - calcium disodium edetate & EDTA) |
| 1 catalyst to oxidation reactions
2 preparations are packaged in __ containers | 1 Light and high temperature
2 light resistant or opaque |
| In summary, easily oxidizable drugs may be
stabilized in formulation by: | selective exclusion from the system of:
1 oxygen
2 oxidizing agents
3 trace metals
4 light
5 heat other chemical catalysis
add to create and maintain a favorable pH:
1 antioxidants
2 chelating agents
3 buffering agents |
| FDA and International Conference on Harmonization | a. Stability Testing of New Drug Substances and Products
b. Quality of Biotechnological Products: Stability Testing of Biotechnology/ Biological Drug Products
c. Photostability Testing of New Drug Substances and Products
d. Stability Testing of New Dosage Forms |
| Scientific data pertaining to the stability
of a formulation leads to: | 1 prediction of the expected shelf-life of the
proposed product
2 redesign of the drug (to more stable salt or ester
form)
3 reformulation of the dosage form. |
| Accelerated testing | 1 Long Term - 25 C (60%) - 12 Months
2 Intermediate - 30 C (65%) - 6 Months
3 Accelerated - 40 C (75%) - 6 Months |
| Elucidate the intrinsic stability of a drug substance
temperature elevations in 10˚ increments higher than used in
accelerated studies - employed until chemical or physical Degradation | Stress testing |
| product is subjected to different climatic zones (temperature & humidity) nationally & internationally
predicted from the data generated from continuing stability studies | Long term stability studies |
| Geographic regions | Zone I- Temperate
Zone II- Subtropical
Zone III- hot and dry
Zone IV- hot and humid |
