Importance of activation energy in drug stability: determination of activation energy of p-nitrophenyle acetate

Drug decomposition or degradation occurs during storage because of chemical reaction of the active ingredients or additives. The knowledge of chemical kinetic is useful to evaluate the shelf life [expiry date] and Stability of drugs. Several factors affecting the reaction rates including the effect of temperature which was quantitatively determined. In this study the hydrolysis of p-nitrophenyl acetate in phosphate buffer pH 8.5 was followed spectrophotometrically by measuring the increase in absorption at 398.5 nm caused by the liberation of p-nitrophenol to determine the activation energy in kilojoules per rmol and Kilocalreis per mole using Arrhinus equation and was found to be 5.27 Kilo calreis/mol. And 22.10 Kilo Joules per mole. Moreover pseudo first-order rate constant for the hydrolysis of p-nitrophenyl acetate was observed

Transdermal delivery of haloperidol: i. effect of vehicles

The influence of vehicles on transdermal delivery of haloperidol from five different vehicles, propylene glycol [PG], water, Glycerin, Liquid Paraffin [LP] and polyethelene glycol 400 [PEG 400] was investigated. It was observed that the highest cumulative amount penetrated in 24 hours in presence of PG [506 microg] compared to the cumulative amount penetrated the skin from the other vehicles used. [113, 58, 24, and 13 microg for water, Glycerin, PEG 400 and LP respectively] indicate that PG could be a good and effective vehicle for transdermal delivery of haloperidol studies. This effect may be related to alteration of the barrier property of the stratum cornium and thermodynamic activity of the drug in the different vehicles. The solubility of haloperidol in these vehicles was also determined. In vitro Improved Franz diffusion cell and dorsal rabbit skin were utilized in the permeation study. Analysis of variance [ANOVA] indicates that, the differences in the cumulative amount obtained from different vehicles were significant p < 0.05. This result suggests that the mechanism of permeation of haloperidol is passive diffusion. In order to determine the parameters which control the diffusion of haloperidol across the excised rabbit skin from propylene glycol solution formulation, the formulation containing concentration of the drug [20mg/ml] was used to a chief a steady-state of diffusion which may be characterized by zero-order kinetic

Bioavailability and in-vivo transdermal delivery of haloperidol

Sustained blood level with effective therapeutic blood level in psychotic patients in the range of usual therapeutic dose is favorable. To investigate where this sustained and effective therapeutic blood level and improve in bioavailability could be achieved by using haloperidol/transdermal gel formulation. In-vivo transdermal delivery of haloperidol was studied in rabbits comparing transdermal gel formulation containing 1, 8-cineole as penetration enhancer and oral tablet. Concentrations of haloperidol in plasma were measured by reverse phase HPLC. The pharmacokinetic parameters generated from this study were evaluated statistically using one-way analysis of variance [ANOVA]. The results showed that transdermal gel formulation increased rate and extent of absorption and improve bioavailability of haloperidol. The plasma concentrations of haloperidol were declined in biexponential fashion where the area under the curves and absorption rate C[max]/AUC elimination rate constant K[el], T[max], mean residence time [MRT], mean absorption time [MAT], and total clearance [CL[total]] were significantly different p < 0.05, but volume of distribution [V[d]] did not differ significantly p >0.05.The absolute bioavailability from the oral tablet, and the transdermal formulation was 38% and 57% respectively and highly significant P < 0.01. This study suggest that it is possible to achieve significant sustained therapeutic blood levels for longer time and also suggest that further human investigations of the transdermal dosage are warranted

In-vitro evaluation of five paracetamol commercial brands available in the Sudan

Literature data are reviewed on the properties of paracetamol related to biopharmaceutical classification. Five leading and competitive commercial products of paracetamol tablets coded as brands A, B, C, D and E [E being the innovator product] in the country were evaluated for their in vitro properties. The study included chemical equivalence, content uniformity, dissolution, disintegration time, friability weight uniformity and resistance to crushing test. All brands pass the in vitro tests as specified in the official monograph with little insignificant variations. Brand A only fail the hardness test. The in vitro data suggested that the dissolution rate release studies could establish bioequivalency of paracetamol tablet and should be done with caution. In conclusion, the above mentioned paracetamol tablets could be reliable to be used safely and effectively especially that the bioequivalence studies in Sudan is not required by the health authority

Percutaneous absorption of haloperidol from different gel polymers through rabbit, human and hairless-mouse skins

Haloperidol is a butyrophenone derivative used for the treatment of psychotic symptoms. This compound is rapidly and almost completely absorbed when taken orally, but the oral bioavailability is about 60% due to extensive first-pass metabolism in the liver. Dorsal rabbit, human and hairless-mouse skins were used to investigate the diffusion properties of haloperidol. The transdermal permeation across full-thickness skins is reported from three polymer gel formulations was investigated using improved Franz-diffusion cells. Gels were prepared containing haloperidol and hydroxypropylmethyi cellulose [HPMC], carbopol 940 and polyethylene glycol mixture. Steady-state flux was rapidly achieved. Zero-order release of haloperidol from these formulations was observed. HPMC was concluded to be a suitable base for a matrix formulation. The reported partition coefficients in this study for human rabbit and hairless-mouse were 0.004, 0.041 and 0.155 respectively. The mechanism of action of the preparations tested were probably due to structural modification of the skin [stratum cornium] or fluidization of the cell contents in the epidermal layer