Effect of additives on the physicochemical properties of liquid suppository bases.
To investigate the effects of additives on the physicochemical properties of in situ gelling and mucoadhesive liquid suppository base, gelation temperature, gel strength and bioadhesive force of liquid suppository base, poloxamer 407 (P 407) and poloxamer 188 (P 188) (15/15%) were evaluated in the presence of following additives: solvent (ethanol, propylene glycol, glycerin), ionic strength-controlling agent (sodium chloride) and pH-controlling agent (hydrochloric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate). Among the additives studied, sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate increased to a great extent the gel strength and the bioadhesive force of P 407/P 188 (15/15%) with a decrease in gelation temperature. Glycerin slightly decreased the gelation temperature and slightly increased the gel strength and bioadhesive force. However, the addition of 1% of sodium chloride, sodium monohydrogen phosphate or sodium dihydrogen phosphate caused a greater than 60-fold increase in gel strength and over a tenfold increase in bioadhesive force with 2-4 degrees C decrease of gelation temperature within optimal range, compared with P 407/P 188 (15/15%) alone. On the other hand, ethanol, propylene glycol and hydrochloric acid increased the gelation temperature and slightly decreased the gel strength and the bioadhesive force. Taken together, these findings indicate that the effect of additives on the physicochemical properties of liquid suppository bases depends on their bonding capacities, in that additives such as sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate having strong cross-linking bonds with the components of liquid suppository base increase the strength and bioadhesive force of a gel compared to liquid suppository base alone, while additives such as ethanol, propylene glycol and hydrochloric acid having weaker hydrogen bonding result in a weaker response. Thus, sodium chloride and sodium phosphates appear to be promising additives for in situ gelling and mucoadhesive liquid suppository base, if used in adequate amounts.
Choi
H
H
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul, South Korea.
Lee
M
M
Kim
M
M
Kim
C
C
D000268:Adhesiveness; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005782:Gels; D005990:Glycerol / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D010710:Phosphates / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013488:Suppositories / Q000737:chemistry*; D013696:Temperature
D005782:Gels; D010710:Phosphates; D012997:Solvents; D013488:Suppositories; D020442:Poloxamer; D000431:Ethanol; D012965:Sodium Chloride; D019946:Propylene Glycol; D005990:Glycerol; D006851:Hydrochloric Acid; C018279:sodium phosphate