Dry Powder Injection
- Majority of drugs show the problem of poor solubility, whether in the case of their analytical estimations or in the
field of liquid dosage forms in the form of solutions.
Commonly used organic solvents for spectrophotometric analysis of water insoluble drugs include methanol, ethanol, chloroform, benzene, dichloromethane, dimethyl formamide, acetonitrile, ethyl acetate, toluene, carbon
tetrachloride, acetone, hexane etc. - The main drawbacks of organic solvents include high cost, toxicity and pollution.
Organic solvents have innumerous adverse effects caused by single exposure like dermatitis, headache, drowsiness,
nausea, eye irritation and long term exposure causes serious effects such as neurological disorders, chronic renal failure, liver damage, necrosis, mutagenesis disorder. - They should be replaced by other eco-friendly alternative sources. The pollution and toxicity caused by most of the organic solvents is a big challenge.
- The researchers are doing much work to give eco-friendly solutions for this challenge.
- Maheshwari has given a nice concept, known as mixed solvency concept. By application of this concept, innumerable solvent systems can be developed.
Maheshwari is of the opinion that each substance possesses solubilizing power. He has given several ecofriendly
methods in the area of drug estimations and formulations precluding the use of toxic organic solvents. - There are very few safe liquids eg. propylene glycol, glycerin, tweens, ethanol, liquid polyethylene glycols (like PEG 200, 300 etc) which are employed by pharmaceutical industries in various dosage forms for making solution type dosage forms of poorly soluble drugs.
- Mixed solvency concept, proposed by Maheshwari provides a means to develop innumerable solvent systems
employing combination of the pharmaceutical excipients in small concentrations. - Each substance present on the earth has got solubilizing power.
- By combining the excipients, additive solvent actions and synergistic solvent actions can be obtained. The problem of toxicity issue due to high concentration of a single solvent can be solved in this manner.
- The solubility of a large number of poorly soluble drugs have been enhanced by mixed solvency concept.
- In the present investigation, the poorly water-soluble drug, candesartan cilexetil, has been selected as a drug for formulating its dry injection for reconstitution by using mixed solvency approach.
Stability of the reconstituted solution or suspension.
- The stability of a PI includes two aspects: the stability of the powder and the stability of the reconstituted suspension or solution. To evolve meaningful post reconstitution utility times, stability data after reconstitution should be generated using all the probable reconstitution solvents at various temperature conditions.
- The reconstituted solutions must be assessed for both physical and chemical stability. Color absorbance sometimes can be used as a quantification tool during early product stability studies.
- The effect of any other medicinal product that is likely to be co administered also should be assessed
- . These stability studies should be carried out at the extremes and median value of product pH.
- Simulation studies in the presence of materials likely to come in contact with the reconstituted injection (e.g., plastic syringes and intravenous tubing’s) also should be conducted to assess their effect on product stability.
The following parameters must be evaluated during the course of accelerated and real-time stability studies:
● Assay and related substances (dry powder and reconstituted suspension)
● Water content
● Discoloration (color absorbance value)
● pH of the reconstituted solution
● pH of the reconstituted product
● Reconstitution time
● Clarity of the reconstituted solution (particulate matter)
● Sterility
● Bacterial endotoxins.
