The effect of selected water-soluble excipients on the dissolution of paracetamol and Ibuprofen.
The purpose of this investigation was to study the dissolution behavior of paracetamol and ibuprofen in the presence of a range of selected potential excipients. First, a pH-solubility profile was generated for both drugs, and the effect of changing hydrodynamic conditions on the intrinsic dissolution rate was investigated. It was established that both drugs dissolved according to the diffusion-layer model. Paracetamol solubility (approximately 20.3 mg mL(-1)) did not vary from pH 1.2-8.0, corresponding to the in vivo range in the gastrointestinal tract. Ibuprofen had an intrinsic solubility of approximately 0.06 mg mL(-1), and pK(a) was calculated as 4.4. Second, the effects of selected potential excipients (lactose, potassium bicarbonate, sodium bicarbonate, sodium chloride, and tartaric acid) were evaluated by measuring the effect of the inclusion of each additive in the dissolution medium on drug solubility, drug intrinsic dissolution rate, and solution viscosity. The results were evaluated using the diffusion-layer model, and it was determined that for paracetamol, the collected data fitted the model for all the excipients studied. For ibuprofen, it was found that there were differences between the excipients that raised the solution pH above the pK(a) to those that did not. For the excipients raising the pH above the pK(a), the effect on intrinsic dissolution rate was not as high as that expected from the change in drug solubility. It was postulated that this might be due to lack of penetration of the excipient into the drug boundary layer microenvironment. Formulators may calculate the effect of adding an excipient based on solubility increases but may not find the dissolution rate improvement expected.
Shaw
Lance R
LR
Medicines Research Unit, School of Life and Health Sciences, Aston University, Birmingham, UK.
Irwin
William J
WJ
Grattan
Tim J
TJ
Conway
Barbara R
BR
D000082:Acetaminophen / Q000737:chemistry / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000493:pharmacokinetics; D001639:Bicarbonates / Q000737:chemistry; D002021:Buffers; D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry / Q000493:pharmacokinetics*; D007785:Lactose / Q000737:chemistry; D008954:Models, Biological; D017680:Potassium Compounds / Q000737:chemistry; D017693:Sodium Bicarbonate / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013644:Tartrates / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014867:Water
D018712:Analgesics, Non-Narcotic; D001639:Bicarbonates; D002021:Buffers; D004343:Drug Implants; D005079:Excipients; D017680:Potassium Compounds; D013644:Tartrates; D014867:Water; D000082:Acetaminophen; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; C026329:potassium bicarbonate; D007785:Lactose; C029768:tartaric acid; D007052:Ibuprofen