PSL Friday Seminar: Guest lecture by Prof. R.K. Maheshwari 21.1.
On this year's first PSL Friday Seminar 21.1. we will have the honor of welcoming Prof. Rajesh Kumar Maheshwari from the Department of Pharmacy, Shri G S Institute of Technology and Science (India) for giving a guest seminar entitled "Solids shall be alternate sources to replace harmful organic solvents in future".
TALK ABSTRACT: Various organic solvents like ethanol, methanol, dimethylformamide, acetonitrile ethyl acetate, toluene, chloroform, benzene, dichloromethane, carbon tetrachloride, acetone, hexane etc. have been employed for UV spectrophotometricestimations of poorly water-soluble drugs. Similarly, various organic solvents like ethanol, methanol, dimethylformamide etc. have been employed for titrimetric estimations of poorly water-soluble drugs. Also, several organic solvents are routinely employed in TLC, HPLC analyses. Drawbacks of organic solvents include higher 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.
Pharmacopoeial (Indian/British) titrimetric analytical methods for bulk drugs of ibuprofen, frusemide, aceclofenac, salicylic acid, ketoprofen, chlorpropamide, phenyl butazone etc involve the use of organic solvents (ethanol, methanol, dimethyl formamide etc). Hydrotropic aqueous solutions of sodium benzoate, sodium acetate, sodium citrate, sodium salicylate, urea, dimethyl urea, niacinamide etc (as well as aqueous solutions of mixed blends of hydrotropic agents) could be employed for such titrimetric analyses precluding the use of organic solvents.
Pharmacopoeial (Indian/British) uv spectrophotometric analytical methods for tablets of tinidazole, atenolol and diclofenac sodium involve the use of a toxic organic solvent, methanol. However, hydrotropic aqueous solutions of sodium benzoate and urea could be used for spectrophotometric analysis of tablets of these poorly water soluble drugs precluding the use of methanol. Tablets/Capsules of a large number of poorly water soluble drugs such as naproxen, famotidine, frusemide, metronidazole, nalidixic acid, hydrochlorothiazide, gatifloxacin, aceclofenac, paracetamol, ofloxacin, norfloxacin, atenolol, diclofenac sodium, piroxicam, tinidazole, ketoprofen etc. have been estimated spectrophotometrically using hydrotropic aqueous solutions of sodium benzoate, sodium acetate, sodium citrate, urea, dimethyl urea, niacinamide etc. (as well as using aqueous solutions of mixed blends of hydrotropic agents) precluding the use of organic solvents.
Maheshwari has proposed the mixed-solvency concept.. The mixed solvency concept states that all substances whether liquid, gas or solid possess solubilizing power. Like solvents (liquids), solids also play very important role in improving the solubilities of drugs in different solvents. A weaker solvent for a particular solute may act as strong solvent for that particular solute in the presence of other solid (in solution form). For example, the solubility of frusemide in ethanol is improved in presence of niacinamide (three times enhancement in solubility in presence of 15% w/v niacinamide in ethanol as compared to solubility of frusemide in ethanol). In order to improve aqueous solubility of a poorly water-soluble drug, the concentrated aqueous solution containing various dissolved excipients (liquids and solids both) can give successful results in solubility enhancement. In one of the studies by Maheshwari it was found that additive and synergistic solvent action on the solubility of salicylic acid could be obtained by using aqueous solutions containing different excipients (liquids and solids both). Mixed-solvency concept shall be helpful to formulate various dosage forms of insoluble drugs utilizing safe concentrations of excipients for solubilization.
Similarly TLC of all the drugs/compounds could be performed using hydrotropic/mixed hydrotropic solutions precluding the use of organic solvents.
Hydrotropy, mixed hydrotropy and mixed-solvency can give alternate solubility enhancement methods in following fields precluding the use of organic solvents:
a) Herbal extractions
b) Herbal formulations
c) Cosmetic preparations
d) Chemical synthesis
e) Purification processes
f) HPLC analysis
g) Dyeing industry
h) Chemical technologies involving solutions of insoluble substances
i) Ink industry
j) Paint industry etc
k) Formulation development of pharmaceutical dosage forms including NDDS
(ii) Solid dispersions of poorly water-soluble drugs
(iii) Liquisolid systems of poorly water-soluble drugs
(iv) Dry powder injection for reconstitution of poorly water-soluble drugs
(v) Dry powder syrup for reconstitution of poorly water-soluble drugs
(vii) Multiple emulsions
(viii) Transdermal gels
(ix) Nasal gels
(x) Oral film of poorly water-soluble drugs
(xi) Vaginal film of poorly water-soluble drugs
NOTE – In all above formulations ( i to xi ), mixed solvency concept is nicely utilized to improve drug loading