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B C Lippold

Publications and source records attributed to B C Lippold.

At least 37 records · Page 2Linked to original sources
PubMed1997

In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: influence of the partition coefficient octanol/water and the water solubility of drugs on their permeability and maximum flux.

Penetration of homologous nicotinic acid esters through the human nail and a keratin membrane from bovine hooves was investigated by modified Franz diffusion cells in-vitro to study the transport mechanism. The partition coefficient octanol/water PCOct/W of the esters was over the range 7 to > 51,000. The permeability coefficient P of the nail plate as well as the hoof membrane did not increase with increasing partition coefficient or lipophilicity of the penetrating substance. This indicates that both barriers behave like hydrophilic gel membranes rather than lipophilic partition membranes as in the case of the stratum corneum. Penetration studies with the model compounds paracetamol and phenacetin showed that the maximum flux was first a function of the drug solubility in water or in the swollen keratin matrix. Dissociation hindered the diffusion of benzoic acid and pyridine through the hoof membrane. Since keratin, a protein with an isoelectric point of about 5, is also charged, this reduction can be attributed to an exclusion of the dissociating substance due to the Donnan equilibrium. Nevertheless, the simultaneous enhancement of the water solubility makes a distinct increase of the maximum flux possible. In order to screen drugs for potential topical application to the nail plate, attention has to be paid mainly to the water solubility of the compound. The bovine hoof membrane may serve as an appropriate model for the nail.

Adult↗
PubMed1997

In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: penetration of chloramphenicol from lipophilic vehicles and a nail lacquer.

Lipophilic vehicles and especially nail lacquers are more appropriate for topical application on the nail than aqueous systems because of their better adhesion. This work has, therefore, studied the penetration through the human nail plate of the model compound chloramphenicol from the lipophilic vehicles medium chain triglycerides and n-octanol and from a lacquer based on quaternary poly(methyl methacrylates) (Eudragit RL). The results were compared with data obtained with a keratin membrane from bovine hooves. If the swelling of the nail plate or the hoof membrane is not altered by use of lipophilic vehicles, the maximum flux of the drug is independent of its solubility in the vehicle and is the same as that from a saturated aqueous solution. These vehicles are not able to enter the hydrophilic keratin membrane because of their non-polar character and so cannot change the solubility of the penetrating substance in the barrier. If the concentration of the drug in the nail lacquer is sufficiently high, the maximum flux through both barriers equals that from aqueous vehicles or even exceeds it because of the formation of a supersaturated system. Penetration through the nail plate follows first order kinetics after a lag-time of 400 h. The course of penetration through the hoof membrane is initially membrane-controlled and later becomes a matrix-controlled process because of the membrane's greater permeability. Chloramphenicol is dissolved in the lacquer up to a concentration of 31%. The relative release rates from these solution matrices are independent of the drug concentration but they decrease on changing to a suspension matrix. These results show that drug flux is independent of the character of the vehicle and that penetration of the drug is initially membrane-controlled and changes to being matrix-controlled as the drug content of the lacquer decreases.

1-Octanol↗
PubMed1995

Enhancing effects of lipophilic vehicles on skin penetration of methyl nicotinate in vivo.

Vehicle effects may be caused by thermodynamic effects and by specific (penetration enhancing) effects. To investigate the effects of various lipophilic vehicles on drug penetration, an in vivo permeability study was conducted with methyl nicotinate as the model drug. The drug was dissolved in the respective vehicles at concentrations that provide equal drug escaping tendencies. Drug solutions were applied to the upper arms of volunteers with a glass chamber system. To avoid drug depletion effects, drug disappearance rates were measured under steady-state conditions by the difference method. Enhancement factors were calculated from the steady-state flux values (i.e., drug disappearance rates per area unit) and compared with results from non-steady-state experiments. Significant enhancing effects (p < 0.01) were observed with dibutyl adipate, caprylic/capric acid triglycerides containing 5% phospholipids, isopropyl myristate, and mineral oil. Caprylic/capric acid triglycerides, cetearyl isooctanoate, and the standard vehicle dimethicone 100 were without effect on drug penetration. The explanation for the observed enhancing effects may be an interaction of the lipophilic liquids with the lipid bilayers of the stratum corneum that leads to a decrease of the barrier resistance.

Adult↗
PubMed1995

Drug release from hydrocolloid embeddings with high or low susceptibility to hydrodynamic stress.

PURPOSE: The subject of the study was the influence of hydrodynamic stress on the drug release from direct compressed hydrocolloid embeddings. Additionally a correlation between the release kinetics and different polymer characterising parameters was attempted. METHODS: The drug release was fitted to an expanded Korsmeyer equation to describe the release kinetics. The influence of the stirring Dissolution Time (MDT) was expressed as quotient of the MDT's at the stirring rate of 200 and 100 min-1. RESULTS: If the drug release followed the square root of time kinetics, nearly no effect of the agitation speed on the release rate was observed. To achieve this diffusion controlled drug release the developing gel layer had to be hydrated very well and resistant against erosion (viscosity of at least 4000 mPa.s of the 2% polymer solution and a small expansion of the swelling gel especially at the beginning of the release). The erosion controlled zero order release was generally much affected by the hydrodynamic stress except for some hydrocolloids with incomplete swelling. Thus, it was possible to define a new release mechanism, the polymer particle erosion. The drug release was controlled by the attrition of partially swollen polymer particles and not by the polymer dissolution or drug diffusion. CONCLUSIONS: Polymer particle erosion or diffusion control should be the release controlling mechanisms for negligible influence of hydrodynamic stress.

Colloids↗
PubMed1995

Absorption of sunscreens and other compounds through human skin in vivo: derivation of a method to predict maximum fluxes.

PURPOSE: The goal of this study was to quantify the transdermally absorbed amounts of the sunscreens octyl dimethyl p-aminobenzoic acid, oxybenzone, 4-isopropyl-dibenzoylmethane, 3-(4-methylbenzylidene)-camphor, isoamyl-4-methoxycinnamate, the repellent and plasticizer dibutyl phthalate, the antioxidant 3.5-di-t-butyl-4-hydroxyanisol, and the antimicrobial compounds butyl-4-hydroxybenzoate, biphenyl-2-ol, and 2,4,4'-tri-chlor-2'-hydroxydiphenylether (triclosane). Permeabilities PB and maximum fluxes Jmax should be correlated with relevant physicochemical properties. METHODS: Saturated solutions of the above-mentioned compounds in a propylene glycol/water mixture were applied to the skin using glass chambers which were fixed to the upper arms of volunteers. Maximum fluxes were calculated from concentration decreases in the vehicle. RESULTS: A linear relationship between the logarithms of permeabilities PB of the penetrants (0.02-0.28 cm h-1) and the corresponding octanol/vehicle partition coefficients PCOct/V (166-186,208) was found. Consequently, the influence of aqueous boundary layers could be neglected. However, the slope of the resulting straight line of 0.38 is considerably smaller than unity indicating that PCOct/V does not represent the lipophilicity of the stratum corneum adequately. Maximum fluxes range from 0.5 to 130 micrograms cm-2 h-1. A general equation for the calculation of Jmax was derived based on experimental data taking into account the PCOct/V and the solubilities CsV of the respective penetrants in the vehicle.

Administration, Cutaneous↗
PubMed1995

An attempt to clarify the mechanism of the penetration enhancing effects of lipophilic vehicles with differential scanning calorimetry (DSC).

In a previous in-vivo skin penetration study, it was observed that certain lipophilic liquid vehicles enhanced drug penetration, whilst others did not. To clarify the mechanism of skin penetration enhancement, isolated sheets of human stratum corneum were measured by differential scanning calorimetry (DSC), either untreated or after pretreatment with various lipophilic liquids (highly purified light mineral oil, isopropyl myristate, caprylic/capric acid triglycerides containing 5% phospholipids, dibutyl adipate, dimethicone 100, cetearyl iso-octanoate, caprylic/capric acid triglycerides), commonly used in ointment bases. All samples were analysed over a heating range of at least--10-130 degrees C. All DSC curves were evaluated with regard to the phase-transition enthalpies (peak areas) and peak maximum temperatures of the lipid-phase transitions at ca 75 and 85 degrees C. With the exception of dimethicone 100, cetearyl iso-octanoate and caprylic/capric acid triglycerides, all vehicles showed characteristic alterations of the phase-transition temperatures and enthalpies of the stratum corneum lipids. Mineral oil and isopropyl myristate caused a reduction of the enthalpy and a decrease of the phase-transition temperatures. These two vehicles are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly partially dissolve the lipids. Dibutyl adipate and caprylic/capric acid triglycerides containing 5% phospholipids decreased the phase-transition enthalpy only, probably due to dissolution or extraction of the stratum corneum lipids. These DSC results provide an explanation for the in-vivo penetration-enhancing effects observed previously.

Calorimetry, Differential Scanning↗
PubMed1994

In vivo skin penetration studies of camomile flavones.

In vivo skin penetration studies of the Camomile flavones apigenin, luteolin and apigenin 7-O-beta-glucoside were carried out with nine healthy, female volunteers. During seven hours the decline of flavonoid concentration in a saturated aqueous alcoholic solution filled in glass application chambers were repeatedly measured by spectrophotometry at fixed time periods. The maximal fluxes were calculated. From the graph of the maximal flux values as a function of time it was concluded, that the flavonoids are not only adsorbed at the skin surface, but penetrate into deeper skin layers. This is important for their topical use as antiphlogistic agents.

Administration, Topical↗
PubMed1993

Zero-order drug release from hydrocolloid matrices.

Matrices are manufactured by direct compression of a powder mixture of a polymer, e.g., methylhydroxypropyl cellulose (MHPC) or polyvinylalcohol (PVAI), and a drug. The following factors that can influence the drug release mode were investigated at constant surface: (i) polymer solution viscosity, glass transition temperature, and swelling; (ii) drug concentration in the matrix and solubility; and (iii) conditions of release experiment (hydrodynamics). In the case of zero-order release profiles (hydrocolloids with low viscosities), only the dissolution of the polymer appears to control the drug release rate. Factors accelerating polymer dissolution resulted in higher release rates. Comparison of swollen and dry hydrocolloid matrices shows that the duration and kinetics of drug release were not controlled by the swelling front moving into the dry polymer, and water penetration and relaxation were not rate controlling. Therefore, the glass transition temperature had no effect on drug release from these hydrocolloids. The higher the hydrodynamic stress exerted on the eroding hydrocolloid, the faster the resulting drug release as a result of accelerated polymer dissolution. With hydrocolloids of very high viscosity the polymer dissolution is slow, and drug release from the swollen gel appears to be controlled by diffusion according to kinetics of the Higuchi type.

Chemistry, Pharmaceutical↗
PubMed1992

How to optimize drug penetration through the skin.

The main problem of the therapy with drugs applied to the skin is the high diffusional resistance of the intact stratum corneum. To increase the flux of a given drug the selection of the vehicle is of utmost importance. Incorporation of the drug at its maximal thermodynamic activity leads to the maximal possible flux, as in vivo studies show with different drugs. The formation of supersaturated solutions and dissociation equilibria as well as drug-vehicle interactions and drug depletion also result from the vehicle selection and influence the flux. The resistance of the stratum corneum is not a constant parameter. It may be reduced by specific vehicle effects, penetration enhancers and hydration. Examples for the increase of drug fluxes are given.

Animals↗
PubMed1989

Influence of drug solubility in the vehicle on clinical efficacy of ointments.

In a bilateral paired comparison (randomized double-blind study) 31 dermatitis patients (atopic and contact dermatitis) were tested with two ointments containing 0.0056% betamethasone-17-benzoate. One ointment was applied on each side of the body. The topical formulations differed in their solution capacities for the drug by a factor of about 50 (solution-type: high mutual affinity between drug and vehicle; suspension-type: low affinity). The different antiinflammatory effects were studied visually by assessing five symptoms: erythema, scaling, infiltration, lichenification, and excoriation. On the 5th day, 73% of the patients showed significant differences between the sides in favor of the suspension-type ointment (Wilcoxon test). Blanching tests on 30 volunteers confirmed the result. The in vitro drug release, however, was faster with the solution-type ointment. The efficacy of an ointment can be increased greatly, if the solution capacity for the drug is low, and thus the partition coefficient between the stratum corneum (barrier of the skin) and the vehicle is high. As long as the barrier is not damaged completely, the difference in drug release is not the determining factor for the effect.

Adolescent↗
PubMed1988

[Determination of critical surface tension--a comparison of 2 methods].

Two methods for the determination of the critical surface tension (gamma c) of pharmaceutical powders are compared: the so called "sinking-technique", which works by measuring the complete sinking of powders in liquids of varying surface tension and the determination of the critical surface tension by measuring the contact angle in dependence on the surface tension of wetting solvent/water-mixtures by means of the sessile drop-technique. The simple sinking-technique gives gamma c-values which only show a moderate degree of agreement with those determined by the sessile drop-technique. Thus the values determined by the sinking-technique are usually 1-3 mN/m higher than those determined by the sessile drop-technique.

Chemical Phenomena↗
PubMed1987

[Filler-controlled release from suspension matrices (laminates)].

The release from a matrix (polyethylenmineral oilgel, Plastibase) with drug (bupranolol) in suspension can be controlled by a controlling layer of the same material which is saturated with the drug. Thus, after a burst period zero order release is reached from the laminate, before square root t-kinetics predominate. The duration of constant release may be extended with fillers in the controlling layer (glass beads, d less than 20 microns). Increasing the thickness of the controlling layer increases both duration of constant release and time to reach it, the latter to a lower extent.

Bupranolol↗
PubMed1984

[In vivo testing of a peroral theophylline depot preparation with zero-order release].

A theophylline depot preparation on the basis of microcapsules (multiple-units principle) with an initial dose Di = 133 mg and a maintenance dose Dm = 217 mg (kof = 22.8 mg/h) is examined after single application to 7 volunteers in comparison with the aqueous solution. The relative bioavailability of the depot preparation is about 92%. Curve fitting shows that the liberation in vivo is clearly slower (kof = 15.6 mg/h) than in vitro. This could be of general importance for the development of peroral depot preparations. Furthermore the data suggest considerable absorption from the large intestine (colon). This is of interest for the conception of peroral preparations with exceptionally long action.

Biological Availability↗