Michael J. Rathbone

University of Otago , Dunedin, Otago, New Zealand

Are you Michael J. Rathbone?

Claim your profile

Publications (14)87.39 Total impact

  • N.J. Medlicott · I.G. Tucker · M.J. Rathbone · D.W. Holborow
    [Show abstract] [Hide abstract]
    ABSTRACT: Two methods for the determination of sample volumes between 0.2 and 0.6 μl were compared by preparing standard curves for volumes over this range. The first method used a Periotron and the second the sample mass. A linear model was fitted and 95% confidence limits for volumes estimated by each method were calculated. This showed that use of either the maximum Periotron reading or the sample mass allowed estimation of volumes to within ±0.056 mUl and ±0.047 mUl respectively. It is proposed that measurement of sample mass provides a simple and accurate method to determine sample volume when analysing drug concentrations at specific sites in the oral cavity.
    No preview · Article · Jun 2006 · Journal of Periodontal Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Films containing 20% w/w chlorhexidine base (particle size 63-125 microm) in poly(epsilon-caprolactone), MW 35,000-45,000, were prepared by solvent evaporation and sections attached to the mesio-lingual and mesio-buccal surfaces of the lower first molar in healthy volunteers. Saliva (<1.5 microl) was collected on Periopaper and chlorhexidine concentrations measured by HPLC were typically higher in the area immediately adjacent to the tooth-bonded film sections and lower at more distant sites. Analysis of variance of chlorhexidine concentrations, adjacent to the film sections, showed concentrations were significantly different on the buccal and lingual sides of the tooth and depended on the time of sampling (n=5, P<0.05).
    No preview · Article · Oct 1999 · Journal of Controlled Release

  • No preview · Article · Sep 1998
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of selected formulation variables on the release of chlorhexidine from poly(ε-caprolactone) films was evaluated in vitro using a complete factorial experimental design. Repeated measures analysis of variance showed chlorhexidine type (diacetate or base), drug load (10, 20 or 30% w/w), chlorhexidine particle size (< 63 or 63−125 μm) and film side (upper or lower) significantly affected the percentage released over 10 and 30 days. Significant interactions were also observed between factors. Release from the upper side of films occurred more slowly than from the lower side of films for most formulations. This difference was particularly apparent for films containing chlorhexidine diacetate. The general release equation (Mt/M∞ = ktn) was fitted to the release data and constants estimated. The value of n, which indicates the mechanism of release, tended towards 0.5 for release at high drug loadings which may suggest release was predominantly diffusion-controlled from these films. Transecting sections of film, prepared with chlorhexidine diacetate < 63 μm (drug loading 20% w/w), and analysing the chlorhexidine content at varying distances from the film surfaces showed a gradient in chlorhexidine concentration through the film, with lower concentrations near the upper side and higher concentrations near the lower side.
    No preview · Article · Oct 1996 · International Journal of Pharmaceutics
  • Natalie J. Medlicott · Ian G. Tucker · Doug W. Holborow · Michael J. Rathbone
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper describes the use of an HPLC assay to investigate whether a chlorhexidine-containing tooth-bonded delivery system produces antibacterial concentrations in the surrounding saliva film. Saliva (<1.5 mu l) was collected from ten sites in the mouth at eight times over a period of four days following application of tooth-bonded delivery systems in two dentally healthy subjects. Analysis of chlorhexidine concentrations in these samples showed a non-uniform distribution of chlorhexidine in the saliva film. Antibacterial concentrations were produced in the area immediately surrounding the delivery system (20 +/- 4 and 28 +/- 12 mu g/ml for Subjects One and Two respectively) whereas concentrations at more distant sites remained low.
    No preview · Article · Jun 1995 · Journal of liquid chromatography
  • N J Medlicott · I G Tucker · M J Rathbone · D W Holborow
    [Show abstract] [Hide abstract]
    ABSTRACT: Two methods for the determination of sample volumes between 0.2 and 0.6 microliters were compared by preparing standard curves for volumes over this range. The first method used a Periotron and the second the sample mass. A linear model was fitted and 95% confidence limits for volumes estimated by each method were calculated. This showed that use of either the maximum Periotron reading or the sample mass allowed estimation of volumes to within +/- 0.056 microliter and +/- 0.047 microliter respectively. It is proposed that measurement of sample mass provides a simple and accurate method to determine sample volume when analysing drug concentrations at specific sites in the oral cavity.
    No preview · Article · Apr 1995 · Journal of Periodontal Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: An HPLC assay for the determination of chlorhexidine in small samples (<1 μl) of saliva is described. A base deactivated reverse phase C-18 narrow bore column (ODS-B Exsil) was used for analysis. Saliva samples were collected on Periopaper strips and chlorhexidine was extracted with 0.1ml mobile phase. The optimal mobile phase comprised 55%v/v acetonitrile, 0.2% v/v glaciel acetic acid, 7mM sodium laurylsulphate and column temperature was maintained at 55°C. Benzethonium was included as the internal standard and a dual wavelength UV absorbance detector was used to analyse chlorhexidine at 254 nm and benzethonium at 275 nm. Triplicate standard curves were linear for the range of concerntration 1 to 15 ng/sample (R2 > 0.09). If 0.5 μl of saliva is collected then 2to 30 μg/ml chlorhexidine can be measured. The intra-assay variability, determined from the repeated injections of quality control standards containing 1, 3.75 and 12.5 ng chlohrexidine/tube was 12.9, 4.4 and 1.5% respectively.
    No preview · Article · Apr 1994 · Journal of liquid chromatography
  • Michael J. Rathbone · Bernadette K. Drummond · Ian G. Tucker
    [Show abstract] [Hide abstract]
    ABSTRACT: Currently there is a high level of interest in the use of the oral cavity as a portal for drug entry to the systemic circulation. As a site for drug delivery the oral cavity offers advantages over the conventional gastrointestinal route and the parenteral and other alternative routes of drug administration. It provides direct entry into the systemic circulation thereby avoiding the hepatic first pass effect, ease of administration and the ability to terminate delivery when required. In addition the membranes that line the oral cavity are readily accessible and exhibit robustness and fast cellular recovery following local stress or damage. The oral cavity appears therefore to be a potential site for the delivery of drugs to the systemic circulation. However, this site is associated with limitations that restrict its use as a route for the systemic delivery of drugs. The low permeability of the membranes that line the oral cavity results in a low flux of drug; there appears to be the need to develop strategies which enhance drug penetration to improve bioavailability. The environment of the oral cavity and the continual secretion and swallowing of saliva are unique problems which need to be considered pre-formulation to ensure successful delivery of a drug via this route. This review highlights the advantages of systemically delivering drugs via the oral mucosa and discusses the membrane, drug, dosage form and environmental issues which limit its use as a site for systemic drug delivery.
    No preview · Article · Feb 1994 · Advanced Drug Delivery Reviews
  • Natalie J. Medlicott · Michael J. Rathbone · Ian G. Tucker · Doug W. Holborow
    [Show abstract] [Hide abstract]
    ABSTRACT: A number of delivery systems have been investigated for administration of antibacterial agents in the treatment of plaque-initiated periodontal disease. These include prolonged release intrapocket devices which are inserted at diseased sites. An effective antibacterial concentration is maintained if drug lost by elimination processes is replaced. Bioassays or sensitive HPLC assays may be used to monitor drug concentrations in the gingival crevicular fluid and allow estimation of the duration of effective release. Non-degradable and degradable systems have been developed, and although improvements in clinical and microbiological parameters are reported with both these systems, advantages have been identified with the degradable systems. Importantly, depleted degradable devices do not require removal at the end of treatment, but repeated administration is generally required, as these systems mostly produce effective drug concentrations for short periods. To improve this method of drug administration the aims and optimal duration of treatment need to be further clarified so that development of delivery system can occur through modification of the device's release and degradation characteristics.
    No preview · Article · Jan 1994 · Advanced Drug Delivery Reviews
  • John A. Weatherell · Colin Robinson · Michael J. Rathbone
    [Show abstract] [Hide abstract]
    ABSTRACT: There have been many attempts to administer drugs locally from devices placed in the oral cavity. The ability to reach a target site following release will be influenced by the ease with which a drug can move around the oral cavity. The rate at which a drug is cleared from that site may influence the magnitude and duration of its effect. Studies suggest that the movement and clearance of substances dissolved or suspended in saliva are complex. In this review we forward explanations for these site-specific patterns and discuss the significance such regional variations may have with respect to the aetiology of oral disease, the placement of delivery systems for optimisation of delivery and in the design and formulation of oral mucosal drug delivery systems used for local delivery of bioactive materials to the oral cavity.
    No preview · Article · Jan 1994 · Advanced Drug Delivery Reviews
  • Michael J. Rathbone · Ian G. Tucker
    [Show abstract] [Hide abstract]
    ABSTRACT: This chapter focuses on reviewing the physicochemical evidence for the mechanism(s) of drug permeation across oral mucosa. It aims to identify those biological and physicochemical parameters which determine the rate and extent of human oral mucosal drug absorption. In addition, the potential barriers that a drug encounters and the possible pathways through which it may traverse the oral mucosa are reviewed. Information pertaining to the mechanism of oral mucosal drug absorption for a given drug, the barrier(s) that it is likely to encounter and the pathway by which it traverses the oral mucosa may (i) provide the rationale for drug candidate selection, analogue synthesis or prodrug design and (ii) provide an insight into methods by which membrane permeability can be modified. Each of these factors may facilitate the optimisation and rational development of drugs and delivery systems for buccal delivery.
    No preview · Article · Oct 1993 · Advanced Drug Delivery Reviews
  • Michael J. Rathbone
    [Show abstract] [Hide abstract]
    ABSTRACT: Two methods were used to study the extent and rate of drug loss from the human oral cavity of some parahydroxybenzoic acid derivatives. Extents of drug loss were measured using the buccal absorption test. Rates of drug loss were measured using a buccal perfusion cell. Both extents and rates of drug loss were shown to be dependent upon alkyl chain length. In addition both showed a similar dependence upon pH. Extents of drug loss were also shown to be independent of initial concentration and the same whether drugs were administered alone or as a multicomponent mixture. Results indicate that oral cavity membranes are essentially lipid in nature and each derivative is lost from the oral cavity by passive diffusion of the non-ionised lipid soluble form in accord with the pH-partition hypothesis. The buccal absorption test is a reliable means of estimating the extent of drug loss from the oral cavity. In contrast, the buccal perfusion cell method provides a simple and reproducible technique for estimating the rate of drug loss from the oral cavity over a fixed area of known membrane under closely controlled conditions.
    No preview · Article · Aug 1991 · International Journal of Pharmaceutics
  • Michael J. Rathbone · Jonathan Hadgraft
    [Show abstract] [Hide abstract]
    ABSTRACT: The rate and extent of drug loss from the human oral cavity can be measured using several different methods. These include the buccal absorption test (Beckett and Triggs, 1967), disc methods (Kaaber, 1974; Schurr and Ziegler, 1983; Pimlott and Addy, 1985) and perfusion cells (Barsuhn et al., 1988, Rathbone, 1990). These methods have provided information on the mechanisms by which drugs are transported across oral cavity membranes and suggest that passive diffusion (Beckett and Triggs, 1967; Beckett and Moffat, 1968, 1969a,b) or carrier-mediated transport systems (Manning and Evered, 1976; Sadoogh-Abasian and Evered, 1979; Evered et al., 1980; Evered and Mallett, 1983; Hunjan and Evered, 1985) may be involved. An appropriate kinetic model to describe the transfer of drugs across oral cavity membranes is problematic (Beckett et al., 1968; Beckett and Moffat, 1970; Beckett and Pickup, 1975; Dearden and Tomlinson, 1971a; Schurmann and Turner, 1978). This is most likely due to the inherent disadvantages associated with the techniques used. Mathematical models describing drug loss from the oral cavity during a buccal absorption test appear equally successful (Ho et al., 1971; Lien et al., 1971; Vora et al., 1972; Wagner and Sedman, 1973). This is despite marked contrast in the underlying assumptions. The object of this review is to evaluate critically the methods available for studying drug loss from the human oral cavity. In addition we review studies which aimed to elucidate the mechanism of drug transfer across human oral cavity mucosa. The review considers literature that has been published since 1967 and highlights areas that appear worthy of further investigations.
    No preview · Article · Aug 1991 · International Journal of Pharmaceutics
  • Michael J. Rathbone
    [Show abstract] [Hide abstract]
    ABSTRACT: A buccal perfusion cell of simple design was constructed and tested. The cell allowed 3.14 cm2 of human buccal membrane to be perfused by 27.5 ml of an aqueous drug donor phase (pH 4.4, 300 mosM/kg) maintained at 37°C. A model drug, butyl p-hydroxybenzoate, was used to evaluate and validate the technique. The kinetics of drug loss from the oral cavity were estimated from knowledge of the change in drug concentration in the aqueous donor phase with time. Fifteen male and fifteen female subjects were employed in the study. Intra-subject variation (n ⩾ 9) for drug loss was shown to be small. Inter-subject variation (n = 30) was shown to be larger than intra-subject variation. No significant difference in the kinetics of drug loss from the buccal perfusion cell were observed between the left and right buccal membrane for any given subject (two-tailed Student's t-test p > 0.05). In addition there was no apparent difference in the rate of drug loss between male and female subjects. The buccal perfusion cell allowed drug transfer across the human buccal membrane to be easily and reliably estimated.
    No preview · Article · Mar 1991 · International Journal of Pharmaceutics