Complexes of zinc, cadmium and mercury with primary aromatic amines
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: Article
- Identifier: vital:6369 , http://hdl.handle.net/10962/d1006070
- Description: We have examined the infrared spectra of thirty-seven complexes derived from the reaction of zinc chloride, mercuric chloride and cadmium chloride, bromide and iodide with several primary aromatic amines. The object of the study was to ascertain whether the frequency data would shed light on the mechanisms of metal-donor atom bonding and electron shifts within the molecules and, in the case of the cadmium complexes, in order to obtain evidence for the transmission of electronic effects through a cadmium atom.
- Full Text:
- Date Issued: 1967
Determination of erythromycin in serum and urine by high performance liquid chromatography with ultraviolet detection
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: text , Article
- Identifier: vital:6428 , http://hdl.handle.net/10962/d1006576
- Description: A high-performance liquid chromatographic analysis of erythromycin in human serum and urine with UV detection at 200 nm is presented. The method involves a solid-phase extraction procedure followed by a simple phase separation step and chromatography on a reversed-phase column. The method has sensitivity limits of 0.25 and 1.0 g/mL in serum and urine, respectively, and is sufficiently sensitive to monitor concentrations of erythromycin in human serum and urine after the administration of a single 500-mg erythromycin stearate tablet.
- Full Text:
- Date Issued: 1985
Determination of phenylpropanolamine in serum and urine by high performance liquid chromatography
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6361 , http://hdl.handle.net/10962/d1006056
- Description: A high-performance liquid chromatographic analysis of phenylpropanolamine in human serum and urine without prior derivatization is presented. Using direct UV detection the method is sufficiently sensitive to detect 25 ng of drug/ml of serum or urine; the coefficients of variation at 25 ng/ml and 500 ng/ml were 5.16 and 2.12, respectively, in serum. The method involves serum and urine extraction at a basic pH with chloroform, a single back-extraction, and chromatography on a reverse-phase column. Serum and urine data following administration of a single 150-mg sustained-release tablet of phenylpropanolamine hydrochloride in 6 healthy volunteers demonstrates the suitability of the analytical method.
- Full Text:
- Date Issued: 1983
Dilution of topical corticosteroid formulations
- Authors: Haigh, John M
- Date: 1988
- Language: English
- Type: text , Article
- Identifier: vital:6377 , http://hdl.handle.net/10962/d1006295
- Description: It has been a long-held concern of a number of people working in this field that some dermatologists prescribing a 1:10 dilution of a corticosteroid preparation such as Dermovate cream believe that the final product will be one tenth as efficacious and also produce one tenth of the side effects as the undiluted formulation. This is certainly not the case. Dermovate falls into the very potent category of topical corticosteroid preparations (as defined in the United Kingdom Monthly Index of Medical Specialities) and a 1:10 dilution falls into the potent category.
- Full Text:
- Date Issued: 1988
Effect of concentration and degree of saturation of topical fluocinonide formulations on in vitro membrane transport and in vivo availability on human skin
- Authors: Schwarb, Fabian P , Imanidis, Georgios , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6425 , http://hdl.handle.net/10962/d1006560
- Description: Purpose. The thermodynamic acitvity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Methods. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Results. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. Conclusions. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.
- Full Text: false
- Date Issued: 1999
Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioeqivalence testing [authors' reply in Letters to the Editor]
- Authors: Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6423 , http://hdl.handle.net/10962/d1006558
- Description: Reply to: Letter to the Editor by Singh GJ; Fleischer N; Lesko L; Williams R - relating to original article in Pharmaceutical Research (USA), Mar 1997, vol. 14, pp. 303-308.
- Full Text: false
- Date Issued: 1998
Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioequivalence testing
- Authors: Demana, Patrick H , Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: Article
- Identifier: vital:6356 , http://hdl.handle.net/10962/d1006047
- Description: The American FDA has recently released a Guidance document for topical corticosteroid bioequivalence testing. The purpose of this study was to evaluate the recommendations of this document for appropriateness. The new specifications require a dose-vasoconstriction response estimation by the use of a Minolta chromameter in a preliminary pilot study to determine the parameters for use in a pivotal bioequivalence study. Methods. The visually-assessed human skin blanching assay methodology routinely practiced in our laboratories was modified to comply with the requirements of the pilot study so that visual and chromameter data could be compared. Two different cream formulations, each containing 0.12% betamethasone 17-valerate, were used for this comparison. Results. Visual data showed the expected rank order of AUC values for most dose durations whereas the chromameter data did not show similar results. The expected rank order of AUC values for both chromameter and visual data was not observed at very short dose durations. In fitting the data to pharmacodynamic models, equivalent goodness of fit criteria were obtained when several different parameter estimates were used in the model definition, however the visual data were best described by the sigmoid E[subscript max] model while the chromameter data were best described by the simple E[subscript max] model. Conclusions. The E[subscript max] values predicted by the models were close to the observed values for both data sets and, in addition, excellent correlation between the AUC values and the maximum blanching response (R[subscript max]) (r > 0.95) was noted for both methods of assessment. The chromameter ED[subscript 50] values determined in this study were approximately 2 hours for both preparations. At this dose duration the instrument would not be sensitive enough to distinguish between weak blanching responses and normal skin for bioequivalence assessment purposes.
- Full Text: false
- Date Issued: 1997
Foam drug delivery in dermatology: beyond the scalp
- Authors: Purdon, Carryn H , Haigh, John M , Surber, Christian , Smith, Eric W
- Date: 2003
- Subjects: Adis International Limited , Drug delivery systems , Skin disorders
- Language: English
- Type: text , Article
- Identifier: vital:6418 , http://hdl.handle.net/10962/d1006541
- Description: Consumers of topical formulations apply a wide spectrum of preparations, both cosmetic and dermatological, to their healthy or diseased skin. These formulations range in physicochemical nature from solid through semisolid to liquid. Pharmaceutical foams are pressurized dosage forms containing one or more active ingredients that, upon valve actuation, emit a fine dispersion of liquid and/or solid materials in a gaseous medium. Foam formulations are generally easier to apply, are less dense, and spread more easily than other topical dosage forms. Foams may be formulated in various ways to provide emollient or drying functions to the skin, depending on the formulation constituents. Therefore, this delivery technology should be a useful addition to the spectrum of formulations available for topical use; however, as yet, only a few are commercially available. Probably the most convincing argument for the use of foams is ease of use by the patient, and consumer acceptance. Most foam dosage forms used in dermatology to date have incorporated corticosteroids, although some products have also been used to deliver antiseptics, antifungal agents, anti-inflammatory agents, local anesthetic agents, skin emollients, and protectants. Although there is no clinical evidence that foam formulations are currently superior to other conventional delivery vehicles, these formulations have a clear application advantage and with continued developments in the science of supersaturation technology, it seems certain that foam delivery systems will retain their place in the dermatological and cosmetic armamentarium.
- Full Text:
- Date Issued: 2003
High performance liquid chromatographic analysis of oleandomycin in serum and urine
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1986
- Language: English
- Type: text , Article
- Identifier: vital:6429 , http://hdl.handle.net/10962/d1006590
- Description: The determination of oleandomycin in serum and urine by high-performance liquid chromatography using erythromycin as internal standard is described. The separation was achieved on a reversed-phase C 1 s column employing acetonitrile-0.05 A4 phosphate buffer (30:70), adjusted to pH 7.0, as the mobile phase with UV detection at 200 nm. A solid-phase extraction procedure, combined with a simple phaseseparation step was used prior to chromatographic analysis. Linear calibration curves were obtained in the concentration ranges 0.25-5.0 pg/ml (serum) and 1 .O-25.0 pg/ml (urine). Precise quantitative analysis has been achieved at these levels with relative standard deviations of < 5%.
- Full Text:
- Date Issued: 1986
In vitro diffusion cell design and validation. I. A stability-indicating high-performance liquid chromatographic assay for betamethasone 17-valerate in purified isopropyl myristate receptor phase
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: text , Article
- Identifier: vital:6431 , http://hdl.handle.net/10962/d1006595
- Description: Introduction: The development of a reliable in vitro permeation system necessitates the use of a precise and accurate method of quantifying the amount of permeant partitioning from the membrane into the cell receptor phase. Aqueous donor and receptor chamber fluids have been used in the majority of reported investigations, which makes quantitative permeant analysis relatively facile. Alternatively, radiolabelled diffusants have been used and flux rates monitored by scintillation counting, obviating the need for chromatographic separation of the receptor-phase components. However, this technique is not applicable when nonlabelled compounds or commercial dosage forms are to be evaluated by a cell system. Furthermore, several studies indicate that aqueous receptor phases may not present an optimal partitioning environment for certain lipophilic permeants (1-4), thereby impairing accurate flux monitoring due to limited diffusant solubility. Several attempts have therefore been made to improve the partitioning environment within these systems, by the addition of surfactants for example (4). A lipophilic receptor environment appears beneficial for corticosteroid partitioning, and thus, the use of isopropyl myristate has been investigated because of its bipolar properties that tend to mimic the biochemical composition of the skin (5,6). Betamethasone 17-valerate and its 21-valerate degradation product are highly soluble in isopropyl myristate and this nonaqueous solvent will not augment C-17-to-C-21 ester degradation reactions.
- Full Text:
- Date Issued: 1989
In vitro diffusion cell design and validation. II. Temperature, agitation and membrane effects on betamethasone 17-valerate permeation
- Authors: Smith, Eric W , Haigh, John M
- Date: 1992
- Language: English
- Type: text , Article
- Identifier: vital:6422 , http://hdl.handle.net/10962/d1006557
- Description: An in vitro permeation cell has been designed and validated for use in monitoring the transmembrane permeation of betamethasone 17-valerate. The design utilizes common laboratory equipment and incorporates as many beneficial features as possible from other designs. The importance of fully validating the hydrodynamic performance of the cell prior to experimentation is stressed. The cell was validated by monitoring the diffusion of betamethasone 17-valerate in isopropyl myristate solution into purified isopropyl myristate receptor phase at different temperatures, different agitation rates and through different synthetic and biological membranes. The results of the hydrodynamic validation agree with data from other researchers and show that the permeation cell is adequately sensitive to these experimental parameters. The results of the membrane evaluation allow appropriate selection of the barrier material for representative transdermal experiments to be conducted. While human and porcine stratum corneum/epidermis are similar in diffusive properties, hairless mouse skin appears to be the most convenient animal membrane for these studies. Although silicone and cellulose membranes appear to be useful in this application, porous filter membranes and egg-shell membranes are insufficiently discriminatory to betamethasone 17-valerate diffusion to provide useful in vitro permeation data.
- Full Text: false
- Date Issued: 1992
In vitro permeation of progesterone from a gel through the shed skin of three different snake species
- Authors: Haigh, John M , Beyssac, E , Chanet, L , Aiache, J M
- Date: 1998
- Language: English
- Type: Article
- Identifier: vital:6366 , http://hdl.handle.net/10962/d1006066
- Description: The in vitro diffusion of progesterone from a gel formulation using the European Pharmacopoeia method for transdermal dosage forms is described. The membranes used were the dorsal and ventral portions of the shed skin of three different species of snake. Considerable differences are apparent between the dorsal and ventral sites and between the different species of snake. The dorsal area shows better permeability for progesterone and the permeability order for the different species is python>cobra>viper. These differences may be due to the thickness of the skin and the hinge:scale ratio. The results indicate that shed snake skin is not a model membrane for human skin.
- Full Text:
- Date Issued: 1998
In vitro release of propranolol hydrochloride from topical vehicles
- Authors: Smith, Eric W , Haigh, John M
- Date: 1994
- Language: English
- Type: text , Article
- Identifier: vital:6435 , http://hdl.handle.net/10962/d1006612
- Description: Transdermal drug delivery is becoming increasingly important and for this reason it is clear that academia must ensure that current graduates are knowledgeable in all facets of topical drug administration. An in vitro diffusion cell experiment was designed to demonstrate the rate of release of propranolol hydrochloride (PHC) from three different topical vehicles: (i) an oil-in-water cream; (ii) a gel; and (iii) anointment. This experiment was performed by final-year students enroled in an undergraduate course on percutaneous absorption. In vitro release of PHC from the three bases to an aqueous receptor phase through silicone membrane was monitored spectrophotometrically at a wavelength of 290 nm. By monitoring and attempting to explain the numerous possible reasons for the different rates of drug release from the three vehicles, it was hoped that the students would gain a better understanding of the complexities of transdermal drug administration. Overall, the experiment would appear to be a good model for student investigation into factors affecting the release of drugs from topical formulations.
- Full Text:
- Date Issued: 1994
In vitro systems for the assessment of drug release from topical formulations and trans-membrane permeation
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
- Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
- Full Text:
- Date Issued: 1989
In vitro-in vivo evaluation of a sustained release phenylpropanolamine oral dosage form
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1982
- Language: English
- Type: Article
- Identifier: vital:6360 , http://hdl.handle.net/10962/d1006052
- Description: There is increasing interest in measuring pharmacokinetic parameters of phenylpropanolamine (PPA), a sympathomimetic amine used in over-the-counter nasal decongestants and anorectic formulations. A high pressure liquid chromatographic (HPLC) procedure was developed to enable direct ultraviolet detection of PPA, after extraction from serum and urine, without prior derivatization of the drug. This method was used to assay samples obtained from a bioavailability study of BUBtained-releasePPA tablets. The mean serum and urine profiles obtained are presented. The sustained-release tablets were subjected to dissolution testing utilizing the United States Pharmacopoeia (USP XIX) rotating basket method. An internal standard was incorporated into the dissolution fluid to enable direct analysis of the samples by HPLC. A comparison of three different dissolution fluid regimens was carried out to determine if release of the drug was affected by the change in pH of the medium and to select the most convenient method for the final dissolution studies. Some preliminary observations relating to correlations between rate of drug release from the sustained-release dosage form and percent drug absorbed are presented.
- Full Text:
- Date Issued: 1982
In vivo/in vitro assessments of topical hydrocortisone availability: correlation between blanching assay and laboratory cell experiments
- Authors: Smith, Eric W , Haigh, John M
- Date: 1995
- Language: English
- Type: Book chapter
- Identifier: vital:6438 , http://hdl.handle.net/10962/d1006624
- Description: From introduction: Topical corticosteroids are still the most widely used drugs in the treatment of dermatological conditions. Early corticosteroid dosage forms consisted of simple creams or ointments where more emphasis was placed on the potency of the drug molecule than on the intrinsic delivery potential of the vehicle. More recently, the effect that the composition of the semisolid base has on the extent of drug delivery has been researched to a much greater extent. These advances in the science of dosage form design have necessitated the refinement of precise and accurate methods for testing the drug delivery efficacies of the developed products. Obviously, the best method for the assessment of the effectiveness of corticosteroid formulations is in a therapeutic situation. Clinical trials, however, are fraught with methodological problems that make duplication of a trial impossible. Alternatively, a number of pharmacological models4 exist for this type of assessment, but it is often problematic to obtain correlation with the true dermatological conditions. The human skin blanching assay is one of the most reliable and reproducible of the ill vivo methods available for the assessment of topical corticosteroid formulations. The skin whitening (blanching or vasoconstriction) side-effect that follows corticosteroid application was first utilized in 1962 as a measure of the percutaneous absorption of corticosteroids from topical formulations. Optimization of this initial procedure7.s has produced a reliable and precise bioassay methodology for the assessment of the efficacy of topical corticosteroid formulations. One criticism of this assay has been the subjective nature of the observation procedure. Although these points have repeatedly been addressed in the literature, it has been suggested that it would be beneficial to have some ill vitro penetration data to supplement ill vivo observations, as this would strengthen the assessment of the topical equivalence of similar delivery formulations. With this objective in mind, a comparison of hydrocortisone release from two proprietary cream formulations was compared by in vivo and ill vitro techniques to determine if any correlation could be established between the methodologies.
- Full Text:
- Date Issued: 1995
Infrared evidence for the transmission of electronic effects through a metal atom in a series of new cadmium complexes
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: text , Article
- Identifier: vital:6371 , http://hdl.handle.net/10962/d1006073
- Description: A series of novel cadmium complexes has been synthesized from the reaction of cadmium chloride, bromide and iodide with primary aromatic amines. The complexes are either mononuclear or polynuclear according to the nature of the halide and amine employed. A possible mechanism for their formation is proposed. The N - H stretching and bending frequencies are linearly related to the electronegativity of the co-ordinated halogen, indicating that the electron withdrawing capacity of the halogen is transmitted through the cadmium atom.
- Full Text:
- Date Issued: 1967
Le test de McKenzie-Stoughton: méthode de mesure de l’effect réservoir
- Authors: Woodford, R , Haigh, John M , Barry, B W
- Date: 1981
- Language: French
- Type: Article
- Identifier: vital:6448 , http://hdl.handle.net/10962/d1006635
- Description: A la suite de I'observation que firent Mac Kenzie et Stoughton en 1962, montrant que I'application locale de cortico'ldes anti-inflammatoires peut produire un blanchiment de la peau, des tests ont ete mis au point pour apprecier la constitution d'une telle paleur chez des sujets volontaires. Les techniques qui ont ete publiees sont variables quant a la methode d'application (avec ou sans occlusion), la duree d'application du cortico'lde (.c'est-a-dire duree breve de 6 a 8 heures ou prolongee de 16 a 20 heures) et quant a la methode d'appreciation de la reponse, enregistree par exemple comme etant presente ou absente, ou bien cotee, soit avec une simple lecture,. soit avec des lectures repetees, pendant un certain temps. Les auteurs ont mis au point des essais standart de vasoconstriction avec et sans occlusion, pour apprecier les preparations quant a leur efficacite clinique pour determiner la biodisponibilite des cortico'ldes a partir des supports pour applications locales. A condition que I'investigateur et Ie volontaire se conforment strictement au protocole du test les methodes suivantes ont une precision surprenante d'appreciation (Barry et Woodford, 1978).
- Full Text:
- Date Issued: 1981
Ligand substitution effects in uranyl ο-hydroxyarylcarbonyl complexes
- Authors: Haigh, John M
- Date: 1974
- Language: English
- Type: text , Article
- Identifier: vital:6372 , http://hdl.handle.net/10962/d1006075
- Description: Twenty-two base adducts of uranyl o-hydroxyarylcarbonyl complexes [UO2L2B] (L = o-hydroxyarylcarbonyl compound, B = H2O, pyridine, pyridine N-oxide) have been prepared. Pure field substituent parameters are used to derive a quantitative order of the electronic effects of the chelate ring substituents. Values of v(U=O) correlate well with these values. Evidence is cited suggesting almost complete non-aromaticity of the chelate ring, and the transmission of the electronic effects of the chelate ring substituent through the uranium atom in the pyridine and pyridine N-oxide base adducts.
- Full Text:
- Date Issued: 1974
New developments in the methodology available for the assessment of topical corticosteroid-induced skin blanching
- Authors: Haigh, John M , Smith, Eric W , Maibach, Howard I
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6384 , http://hdl.handle.net/10962/d1006305
- Description: Since the publication of the previous edition of this book there have been considerable developments and controversy in the field of topical corticosteroid bioequivalence assessment. There has been considerable discussion in the literature concerning the use of the Minolta chromameter for the measurement of corticosteroid-induced skin blanching, as it is believed this instrument would produce more objective results than the visual grading procedure. These efforts culminated in the release of a guidance document from the Food and Drug Administration (FDA) detailing the procedures to be followed for the determination of topical corticosteroid bioequivalence using the chromameter. Since the promulgation of this document there have been challenges on the validity and scientific merit of the documented procedures, and recently the FDA itself conceded that it may be necessary to redefine some of the protocol evaluations. This chapter attempts to redefine the current standing of the two methods of response assessment.
- Full Text:
- Date Issued: 1998