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Solid-state interaction between ibuprofen and nicotinamide was studied using thermal, spectroscopic, and microscopic techniques. Solubility enhancement was calculated by high-performance liquid chromatography and suspension was found to be the suitable choice of formulation. Ibuprofen-nicotinamide binary mixtures were prepared by solvent evaporation method. Differential scanning calorimetry was used to investigate the stoichiometry and thermal properties of the complex between ibuprofen and nicotinamide. A sharp, single endotherm was observed between the melting endotherms of the individual components at a composition of 60% ibuprofen and 40% nicotinamide (w/w). Several spectroscopic techniques such as ultraviolet-visible, Fourier transform infrared, nuclear magnetic resonance, and powder X-ray diffraction were used to investigate the type of interaction between the two components. Optical microscopy was performed to observe changes with regard to particle size and crystal habit. It was concluded that the interaction that occurred was Pi donor-Pi acceptor in nature and too weak to sustain the integrity of the complex in the liquid state. The solubility of ibuprofen was enhanced by 62 times in the suspension when the concentration of nicotinamide was 13.3 mg/mL. The suspension prepared in this study has potential of being a better medication for pain relief in patients with osteoarthritis.

The present study evaluates the effects of excipients, compression pressure, and relative humidity (RH) on the stability of sulfamerazine polymorphs (referred here as SMZ I and SMZ II) and their release from directly compressed tablets using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution analysis. SMZ I and SMZ II tablets were compressed with magnesium stearate (MGST), and microcrystalline cellulose (MCC) at 5000, 7500, and 10,000 lbs. pressures and stored at 40, 75, 95, and 100% RH conditions for 5 weeks. There were indications of possible drug-excipient interaction in the binary mixtures under different relative humidity conditions from the DSC data, but they could not be confirmed by PXRD because the crystal structures of the drug and excipients remained unaltered. The crystal structures of the polymorphs in the tablet also remained unaltered under the above conditions. There were, however, significant differences observed in the drug release properties of the two polymorphs. SMZ II was found in general to have a higher rate of drug release than SMZ I. Extensive gelation of MCC under higher moisture conditions, compression pressure during tableting, and inherent tabletability of the sulfamerazine crystals were factors that affected drug release. All these factors contributed towards prolonging the disintegration and deaggregation of the tablet particles and were therefore concluded to be the rate limiting steps for the dissolution process.

The objective of this study was to develop and analyze an analytical method in order to evaluate preformulation candidates by their thermodynamic parameters and evaporation characteristics. Ortho, meta and tere-phthalic acids were chosen as model compounds. The relative advantages and disadvantages of a rapid thermogravimetric method have been studied in detail, which would aid in the preformulation characterization for pharmaceuticals. Methyl paraben was taken as the model compound for calibration, as its evaporation characteristics are well known. Using the Antoine and the Langmuir equation for evaporation conjointly, the parameter k, known as the coefficient of evaporation was determined. The value for this constant was validated by three methods simultaneously. Previously the use of such methods for compounds having uninhibited zero order evaporation has been documented. In the present study, phthalic acid was chosen as the model compound since its evaporation is a two-step overlapping phenomenon. In this study we have shown the use of Pressure Differential Scanning Calorimetry in separating such simultaneous endothermic processes. The Clausius-Clapeyron equation seemingly has anomalous behavior for vapor pressure over high temperature ranges. In this study a modification of the equation has been suggested to take into account the changes in the heat capacities that result due to high temperature effects. This study aims at documenting a concise method for rapid pharmaceutical characterization and suggests modifications for some basic thermodynamic parameters over higher temperature ranges.

Sedimentation of dilute pharmaceutical suspensions obeys Stokes's law, which assumes that there is no interaction between particles. The behavior of concentrated pharmaceutical suspensions is generally interpreted by use of modifications of Stokes's law that do not consider chemical interaction between particles. Properties of the medium itself, such as dielectric constant and surface tension, have not been included in the established equations. The present work shows that the dielectric constant of the medium has a distinct effect on the rate of sedimentation of the systems investigated.

Many pharmaceutical formulations are produced in the form of concentrated suspensions. Calcium carbonate suspensions are used in this study and interpreted as the “model” for the behavior of such suspensions. The behavior of concentrated suspensions of powders in a liquid medium cannot be treated by the simple application of the normal principles of free fall and the use of Stokes Law pertaining to the viscous resistance offered by the surrounding fluid to fall. A single particle operating by the Stokes principle obeys this relationship. This law applies to the behavior of particles at low concentration in a liquid medium and is the basis for particle size distribution methods. At higher concentrations, however, the particles do not enjoy the freedom of unhindered fall. The system subsides “en bloc” and it is common practice to offer a modification to the Stokes equation which takes into consideration some function of the porosity of the system. There have been a considerable number of equations developed and modified based on this principle. However, an alternative method is to approach the problem by dealing with the permeability of a bed of powders in a liquid in which the bed is slowly altering with time. This is best achieved by the use of the permeability equation developed and presented by Kozeny–Carmen. This equation, as well as the Richardson–Zaki expression, are related to show that the Kozeny parameter K varies with the suspension porosity under sedimentation conditions. The values of K are often larger than the value normally reported (i.e., ~5). The data and treatment outlined here are extended to include not only the calcium carbonate suspensions, but other systems previously mentioned in the literature.

The solubility of a series of compounds was determined in a wide polarity spectrum of normal aliphatic alcohols over a limited temperature range. The solutes chosen were the methyl through n ‐butyl p ‐hydroxybenzoates, several of these being useful preservatives. Solubility profiles were determined for these compounds and the effect of temperature upon their solubility behavior was investigated. The solubility of the solutes is expressed in several concentration notations; mole fraction plots showed a variable twin peak array as a function of the dielectric constant for the solutes studied. Since heats of fusion were available and data were generated as a function of temperature, ther‐modynamic parameters for these systems could be calculated. The relationship of these parameters to multiple solubility peak array is discussed.

Molecular orbital calculations were carried out on the series benzoic acid, p -hydroxybenzoic acid, methylparaben, and ethylparaben. The characteristic trends of this entire series of preservatives are demonstrated by these members. The computer program used was Iterated Extended Huckel Theory. These systems were characterized in terms of atomic charge distributions, effect of hydroxyl and ester groups (both sterically and electronically), preferred molecular conformations, and distinguishing features of molecular orbitals. Through this approach, it was hoped that a common mode of action for all members of this series could be detected and that the trend(s) in this feature would correlate with known trends in activity of members of this series.

The solubilities of a series of chemically related barbiturates, including some medically useful ones as well as phenobarbital, were determined at 25 degrees in the straight-chain alcohols methanol through butanol. The solubility values are given in both milligrams per milliliter and the mole fraction notation. The solubility in methanol was the highest and decreased nonlinearly for the solubility in 1-butanol. In several cases, mole fraction solubility gave shouldering or peaking as a function of the carbon number of the solvent. This series of barbiturates was broken down into two subsets of straight-chain and branched alkyl barbiturates, and solubility ratios in these subsets were considered.

It has been shown that the degradation of aspirin in mixtures may be monitored by thermal analytical techniques. The methodology employed differential scanning calorimetry and thermal gravimetric analysis by standard techniques providing simple and rapid analysis for screening the stability of aspirin in mixtures. The degradation was found to depend on the nature of the additive but, in particular, the presence of acidic or basic groups within its structure.

The solubility of a related series of parabens was determined in water at four temperatures. The parabens chosen were the methyl through n-butyl p-hydroxybenzoates, and the temperature variations were 5 degrees increments from 25 to 40 degrees. These solutes are useful preservatives, especially combinations of the methyl and propyl ester derivatives. The chemical relationship of these compounds varied by successive linear methylene additions on the ester portion of the molecules. The thermodynamic values obtained for these aqueous systems could be related to these molecular variants since the remainder of the molecule was constant. For the overall thermodynamics, the free energy functions such as the ideal, actual, and excess were found to be smooth, nonlinear functions of the number of carbon atoms in the alkyl portion of the paraben esters. A linear relationship with the number of carbon atoms in the ester portion of these esters was found with the partial excess free energy of the solute.