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Biomedical subjects

J Hadgraft

Publications and source records attributed to J Hadgraft.

84 records · Page 5Linked to original sources
PubMed1981

Thermodynamics of partitioning and efflux of phenothiazines from liposomes.

The partitioning of nine phenothiazines between dimyristoylphosphatidylcholine (DMPC) liposomes and 0.9% wt/vol saline at pH 6 has been studied both below and above the phase transition temperature (Tc) of the phospholipid. Higher partitioning was observed above Tc. Both the entropy and enthalpy of partitioning were positive below and above Tc, and a linear relationship between the entropy and enthalpy has been derived. In general, the partitioning and transport of alkylaminophenothiazines in DMPC liposomes over the temperature range of 5 to 40 degrees C is entropically controlled. The entropies and enthalpies of partitioning of various groups in the phenothiazine structure have been calculated. No relationship was found between particle size of the DMPC liposomes and the equilibrium partition coefficient at 25 degrees C. However, the particle size of liposomes did increase with increasing acyl chain length of the phospholipid. Using differential scanning calorimetry, the enthalpy and entropy of transition of the DMPC liposomes in the absence and presence of phenothiazines has been calculated. The temperature dependence of the first-order rate constant of trimeprazine tartrate transport in DMPC liposomes was investigated and was found to be maximum at the Tc of the phospholipid.

Dimyristoylphosphatidylcholine↗
PubMed1980

The interaction of mequitazine with phospholipid model membranes.

The effect of increasing concentrations of mequitazine, a quinuclidinylmethyl-phenothiazine, on the phase transition temperature (Tc), the broadening of the transition peak, the enthalpy and entropy of transition of dimyristoyl-, dipalmitoyl- and distearoylphosphatidylcholine (DPPC) liposomes was studied. Pest critical micelle concentrations of mequitazine (CMC = 5.23 X 10(-2) M), caused broadening of the transition peak and lowering of the Tc of pure liposomes. The ratio of peak heights from the nuclear magnetic resonance (NMR) spectra of egg phosphatidycholine liposomes was used as a criterion for assessing the interaction of the drug with phsopholipid membranes. Mequitazine interacts with both the polar head groups and hydrophobic membrane interior.

Calorimetry, Differential Scanning↗
PubMed1979

Percutaneous absorption: interfacial transfer kinetics.

A new rotating diffusion cell is described in which a solute diffuses through a rotating filter. The transport of the solute to both sides of the filter is controlled by the rotation. The filter is filled with an organic phase. The rate of transfer of the solute through the filter is determined by the transport and by the kinetics of the interfacial transfer reactions. Since the transport is controlled the rate constant for the transfer reaction can be measured. Results for eleven different systems are reported and it is found that the rate constants are all smaller than 10(-4) ms-1.

Diffusion↗
PubMed1979

Percutaneous absorption: theoretical description.

Equations are derived to describe the percutaneous absorption of a substance through the epidermal barrier. The treatment includes interfacial barriers and allows for the depletion of the substance in the external phase. The equations are derived both for the continuous application and for pulse experiments where the drug is applied for a time, then removed, and the response occurs some time after the removal of the drug. Competition between the drug diffusing through the keratinized cells (transcellular route) and diffusing in the interstitial channels around the cells (intercellular route) is also considered.

Kinetics↗
PubMed1979

Percutaneous absorption: in vivo experiments.

The percutaneous absorption of esters of nicotinic acid has been studied in vivo in man. The time for erythema to be produced has been measured both when the ester is applied continuously and in 'pulse' experiments when the ester is removed before the erythema develops. The results show that the erythema is produced long before steady state diffusion across the epidermis is established and the penetration of methyl nicotinate is characterized by D/l2 = 2.3 X 10(-4)s-1 where D is the diffusion coefficient and l the thickness of the barrier. Results using glycerol water mixtures in the external phase show that the route of penetration for methyl nicotinate is through the interstitial channels and not through the keratinized cells. Data for absorption from various creams and ointments (Barrett et al 1964) show that the route is independent of the nature of the external phase. Steady state data for the absorption of salicylic acid and carbinoxamine through the abdominal skin of guinea-pigs (Arita et al 1970) show that the route of penetration does not change as the experiment proceeds. Data for the absorption of other substances (Michaels et al 1975) also fit the interstitial route.

Diffusion↗
PubMedDate not supplied

Recent developments in topical and transdermal delivery.

Over the past decade there has been considerable interest shown in an understanding of the mechanisms of skin penetration and its enhancement. Sophisticated biophysical techniques have been used to probe, at a molecular level, the ways in which chemical and physical enhancement can be achieved. Two types of chemical penetration enhancers can be identified and their co-administration can result in synergistic effects. Another attractive method for enhancing skin penetration is the use of supersaturation but problems associated with stability must be addressed. Biotech drugs are inherently difficult to administer and recent progress using iontophoresis and sonophoresis has identified that medicines of this type can be delivered percutaneously. It is also possible to use the percutaneous route to monitor plasma levels non-invasively. Coupling non invasive monitoring with controlled delivery allows the possibility of creating transdermal systems which act with bio feedback.

Administration, Cutaneous↗
PubMedDate not supplied

Predicting the dermal absorption of thalidomide and its derivatives.

Concern has been expressed about the ability of simple algorithms to predict skin permeability and hence skin flux. For a series of thalidomide analogues, a number of software packages have been used to predict octanol water partition coefficients. These, in conjunction with molecular weight, have then been used to calculate skin permeability coefficients. These compare favourably with experimental values. Some of the software packages also predict aqueous solubilities, which can be subsequently used to calculate maximum skin flux. The predicted and measured solubilities have been compared together with the maximum fluxes. The results show that software can be used to predict octanol water partition coefficients and aqueous solubilities (more accurately if the melting point of the compound is known) and hence to obtain very reasonable estimates of skin permeation parameters. These are useful in predicting which analogue has the most appropriate properties for dermal delivery; in the case of the thalidomide analogues, it is the methyl-substituted compound that is best.

Administration, Cutaneous↗
PubMedDate not supplied

Skin penetration of topical formulations of ibuprofen 5%: an in vitro comparative study.

An in vitro isolated human skin technique with known reliable predictive value for in vivo performance was used to compare the skin penetration of the proprietary ibuprofen gel formulation, Ibugel, with five other commercially available topical formulations containing ibuprofen 5%: Ibuspray, Ibumousse, Proflex Cream, Fenbid Gel and Deep Relief Gel. There was a marked difference between some formulations in the percentage of applied ibuprofen penetrating the skin samples, with Ibuspray, Ibugel and Ibumousse showing the most efficient penetration. The percentage of applied ibuprofen penetrating the skin samples from these formulations was significantly greater (p < 0.05) at all sampling intervals when compared with Proflex Cream, Fenbid Gel or Deep Relief Gel. By 48 h, the percentage of applied ibuprofen that had penetrated through the skin samples from Ibuspray, Ibugel and Ibumousse was approximately 2.5 times greater than that from Deep Relief Gel, 3 times greater than that from Proflex Cream and 5 times greater than that from Fenbid Gel. The data demonstrate that, with topically applied preparations, the composition of the vehicle can have a significant impact on the percutaneous penetration of the active medicament. The possible reasons for this are discussed in terms of partition and diffusion phenomena. Different topical presentations of the same drug substance--especially agents like ibuprofen which are intended for subcutaneous action--cannot be assumed to be pharmaceutically and clinically equivalent or indeed interchangeable.

Administration, Cutaneous↗