Lipophilic Matrices Research Articles

Formulation and Evaluation of Naringin Loaded Transdermal Patches using 32 Full Factorial Design

The main goal of the current study was to maximize the bioavailability of naringin by prolonging the drug’s release using transdermal patches. Ethyl cellulose (EC) served as the lipophilic component and hydroxy propyl methyl cellulose (HPMC) as the hydrophilic matrix in the preparation of transdermal patches. A 32-complete factorial technique was used to build the optimal design matrix, altering the ratio between the hydrophilic and lipophilic matrices. To create the best optimum formulation, three alternative ratios of EC and HPMC were employed. The patches had pH values ranging from 5.28 ± 0.006 to 5.62 ± 0.015. The transdermal patches had thicknesses ranging from 0.514 ± 0.004 to 0.697 ± 0.004 mm. The average weight of the prepared transdermal patches ranged from 194.67 ± 0.578 to 241.67 ± 1.528 mg. The transdermal patches’ moisture content ranged from 7.23 ± 0.158 to 10.33 ± 0.158%. Tensile strength values of the prepared transdermal patches ranged from 9.59 ± 0.006 to 10.41 ± 0.035 kg/cm2, while the drug content varied from 94.7 ± 0.6 to 97.33 ± 0.208%.

Preparation and evaluation of ciprofloxacin solid dispersion tablets developed from stearic acid, Polyethylene Glycol 4000 and Soluplus

Ciprofloxacin is a fluoroquinolone antibiotic with a broad spectrum of activity used for the treatment of various bacterial infections and is characterized by poor aqueous solubility and low permeability. The aim of this study is to formulate and characterize ciprofloxacin solid dispersions using hydrophilic and lipophilic matrices for improved product qualities and drug delivery. Ciprofloxacin hydrochloride tablets were formulated as solid dispersions by melting and solvent evaporation in tablet moulds using varying concentrations of stearic acid (10-40 %w/w), Polyethylene glycol 4000 (PEG 4000) (10-40 %w/w) and Soluplus® (10-20 %w/w as ethanolic solution) as components. The prepared tablets were evaluated for weight uniformity, friability, hardness, Fourier transform-infrared spectroscopy (FT-IR), moisture uptake, swelling index, disintegration time and dissolution rate, using standard methods and optimization techniques. The results showed uniform solid dispersion weights with friability, hardness, moisture uptake and swelling index of 0.4-0.5%, 3.0-7.5 kgf, mostly <20% and 1-71%, respectively. The formulations were chemically stable with no transformational interactions between components. Formulations without stearic acid disintegrated within 30 min whereas those containing the lipid broke up after more than 1 h. Drug release studies showed high immediate release in tablets without stearic acid but with cumulative steady state release higher in formulations with 10 %w/w Soluplus and different concentrations of stearic acid and PEG 4000. In conclusion, ciprofloxacin was presented as solid dispersion tablets with modified physicochemical attributes for improved drug delivery.
 Keywords: Ciprofloxacin; solid dispersion; drug delivery

Enzymatic Acylation of Flavonoids from Bamboo Leaves: Improved Lipophilicity and Antioxidant Activity for Oil-Based Foods.

The goal of this study was to expand the applications of bamboo leaf flavonoids (BLFs) by improving their lipophilicity through enzymatic acylation with vinyl cinnamate. Characterization of the acylated BLFs using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, high-resolution electrospray ionization mass spectrometry, electrospray ionization with tandem mass spectrometry, and 1H nuclear magnetic resonance spectroscopy indicated that acylation occurred at the C6-OH position of glucoside moieties. The highest degree of acylation (18.61%) was obtained by reacting BLFs with vinyl cinnamate (1:5, w/w) at 60 °C for 48 h. Acylation significantly improved the lipophilicity of BLFs and their capacity to inhibit lipid peroxidation, as evidenced by the reduced production of lipid hydroperoxides and malondialdehyde in rapeseed oil and rapeseed oil-in-water emulsions during storage at 37 °C for 15 days. The study findings provide important data that will enable the use of BLFs in lipid or lipophilic matrices, such as oil-based foods.

Encapsulation of the Antioxidant Tyrosol and Characterization of Loaded Microparticles: an Integrative Approach on the Study of the Polymer-Carriers and Loading Contents

Tyrosol, a powerful antioxidant present in high amounts in olive oil and mill wastes, possesses relevant health benefits due to its antioxidant properties. Therefore, tyrosol is a promising compound for further incorporation in functional foods. However, its incorporation in food matrices is limited due to its hydrophilicity. Therewith, encapsulation by double emulsion solvent evaporation emerges as an alternative for its protection and incorporation in lipophilic matrices, as some foods. This work aimed to encapsulate tyrosol in alternative carriers—poly(D,L-lactide-co-glycolide), ethylcellulose, and polycaprolactone, using two theoretical loading contents (TLC) (5% and 10% w/w). Tyrosol was efficiently incorporated in the selected polymer-carriers. Significant effects of the TLC were found on the product yield, encapsulation efficiency, thermal stability, morphology, and on the particle size distribution. This is the first study regarding the encapsulation of tyrosol and brings new insights concerning the encapsulation of antioxidants for further incorporation in food matrices.

Improvement of the Color Stability of Cyanidin-3-glucoside by Fatty Acid Enzymatic Acylation.

Anthocyanins are water-soluble pigments with limited application in lipophilic matrices such as lipid-based foods and cosmetic formulations. In this work, the liposolubility improvement of cyanidin-3-glucoside (cy3glc) was performed by enzymatic esterification with saturated fatty acids with variable chain lengths, and their thermostabilities were evaluated at different pH values in a lipophilic medium (an aqueous sodium dodecyl sulfate solution) by means of UV-vis spectroscopy. Overall, lipophilic cy3glc derivatives showed improved color stability and lowered sensitivity to thermal degradation than nonmodified cy3glc in an SDS micellar solution between pH 3 and 7.

A Green and Rapid Analytical Method for the Determination of Hydroxyethoxyphenyl Butanone in Cosmetic Products by Liquid Chromatography

An analytical method for the determination of hydroxyethoxyphenyl butanone, which is used as an alternative preservative in cosmetic products, has been developed and validated for the first time. The method is based on a simple ultrasound-assisted lixiviation of the analyte from the cosmetic matrix followed by liquid chromatography with UV spectrophotometric detection. Under optimized conditions, the method limit of detection and limit of quantification values were 30 and 90 µg·g−1, respectively. The method was validated with good recovery values (86–103%) and precision values (RSD 0.2–4.7%). Finally, the proposed analytical method was successfully applied to 7 commercially available cosmetic samples including both lipophilic and hydrophilic matrices, such as moisturizing cream, sunscreen, shampoo, liquid hand soap, and make-up. Additionally, a laboratory-made cosmetic cream containing the target analyte was prepared and analyzed. The good analytical figures of merit of the proposed method, in addition to its environmentally-friendly characteristics, demonstrate its usefulness to perform the quality control of cosmetic products to ensure the safety of consumers.

Extending the stability of red and blue colors of malvidin-3-glucoside-lipophilic derivatives in the presence of SDS micelles

Anthocyanins lipophilization recently emerged as an efficient tool to deliver oil-soluble dyes aiming to expand their applications in lipophilic matrices such as cosmetics formulations. Sodium dodecyl sulfate (SDS) micelles were used to solubilize malvidin-3-glucoside derivatives bearing an ester chain derived from dodecanoic and hexanoic fatty acids. Detailed investigations on the kinetic and thermodynamic behavior of the pigments towards pH variations was carried out by means of UV-Vis spectroscopy. It was found that the pH domain of the red flavylium cation is extended in ca 0.3–0.4 pH units. The mole fraction of the quinoidal base at neutral conditions increased by 40% when compared with malvidin-3-glucoside in the same micellar media, which provides a great blue color stabilization. The results presented herein report for the first time the blue color stabilization of these lipophilic anthocyanin bioactives, opening new application fields as novel colorants for lipid-based foods and cosmetics.

Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro–in silico approach

Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro–in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro–in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.

Different magnesium release profiles from W/O/W emulsions based on crystallized oils

Water-in-oil-in-water (W/O/W) double emulsions based on crystallized oils were prepared and the release kinetics of magnesium ions from the internal to the external aqueous phase was investigated at T=4°C, for different crystallized lipophilic matrices. All the emulsions were formulated using the same surface-active species, namely polyglycerol polyricinoleate (oil-soluble) and sodium caseinate (water-soluble). The external aqueous phase was a lactose or glucose solution at approximately the same osmotic pressure as that of the inner droplets, in order to avoid osmotic water transfer phenomena. We investigated two types of crystallized lipophilic systems: one based on blends of cocoa butter and miglyol oil, exploring a solid fat content from 0 to 90% and the other system based on milk fat fractions for which the solid fat content varies between 54 and 86%. For double emulsions based on cocoa butter/miglyol oil, the rate of magnesium release was gradually lowered by increasing the % of fat crystals i.e. cocoa butter, in agreement with a diffusion/permeation mechanism. However for double emulsions based on milk fat fractions, the rate of magnesium release was independent of the % of fat crystals and remains the one at t=0. This difference in diffusion patterns, although the solid content is of the same order, suggests a different distribution of fat crystals within the double globules: a continuous fat network acting as a physical barrier for the diffusion of magnesium for double emulsions based on cocoa butter/miglyol oil and double globule/water interfacial distribution for milk fat fractions based double emulsions, through the formation of a crystalline shell allowing an effective protection of the double globules against diffusion of magnesium to the external aqueous phase.

The nonlinear effect of alkyl chain length in the membrane interactions of phenolipids: Evidence by X‐ray diffraction analysis

Despite the evidence supporting a relationship between phenolipid's alkyl chain length and their interaction/affinity with membranes, such a connection has not been directly evaluated. In this study, the membrane interactions of rosmarinic acid, and its corresponding alkyl esters having 4 carbon (RC4), 8 carbon (RC8), 10 carbon (RC10), and 16 carbon (RC16) have been investigated via small angle X‐ray scattering (SAXS) approaches in model membrane liposomes. The results of this work show significant differences between the tested phenolipids with respect to their interaction and location within the lipid bilayer. Both membrane affinity and penetration depth follow a nonlinear behavior. They have been shown to increase as a function of increasing alkyl chain length until a threshold is reached for medium alkyl chain, beyond which any lengthening of the chain results in a collapse. RC8 show the highest affinity for the membrane, whereas RC10 constitute a critical chain length from which the penetration depth decreases. The X‐ray scattering analyses seem to perfectly correlate with the phenolipids’ activities (antioxidant and membranes crossing) previously observed both in biological system and in formulated lipid dispersions.Practical applications: Phenolic compounds are potent antioxidants that may play an important role as well in biological system as in formulated lipid dispersions. However, their activity is often limited by low solubility or bioavailability. Lipophilization of phenolic compounds may increase their solubility in lipophilic matrices, conferring better antioxidant protection for food or nonfood application. In biological system, lipophilization may contribute to easier penetration of antioxidants through lipid bilayer of cell membranes, which can significantly increase their bioavailability. Despite the evidence supporting a relationship between phenolipid's alkyl chain length and their interaction/affinity with membranes, such a relationship has not been directly evaluated. Investigation of membrane interactions between phenolic and its lipophilic derivative, via SAXS approaches in model membrane liposomes, provide new knowledge about this class of compound with the perspective to be used as substances with maintained or improved biological properties for food, cosmetic and pharmaceutical applications.An X‐ray diffraction analysis highlighted different membrane affinity and nonlinear penetration depth of a series of phenolipids (rosmarinic acid, and its corresponding alkyl esters having 4 carbon (RC4), 8 carbon (RC8), 10 carbon (RC10), and 16 carbon (RC16)). The results seem to perfectly correlate with the phenolipids’ activities (antioxidant and membranes crossing) previously observed both in biological system and in formulated lipid dispersions.

Regioselective synthesis of diacylglycerol rosmarinates and evaluation of their antioxidant activity in fibroblasts

A series of new model of lipophilized phenolic compound derived from the rosmarinic acid was synthesized: 1,2‐diacylglycerol rosmarinate (RDAG) with different alkyl chain lengths from five to eighteen carbons. These RDAG were obtained through a chemo‐enzymatic synthesis: A chemical esterification based on the Mitsunobu reaction, followed by a lipase‐catalyzed transesterification to link the different lipophilic moieties. The antioxidant abilities of these molecules were assessed on reactive oxygen species (ROS) overexpressing fibroblasts. The RDAG12 displayed the best antioxidant activity of the series. Lengthening of the lipid chain beyond twelve carbon atoms leads to a decrease in the antioxidant activity, thus confirming the occurrence of a cut‐off effect. Antioxidant RDAG12 activity was then compared with that of vitamins C and E, rosmarinic acid and decyl rosmarinate (R10). The order of activity was R10 > RDAG12 > RDAG5 > rosmarinic acid ∼ vitamin C ∼ vitamin E. At 5 μM, R10 exhibited an even better antioxidant activity than the combination of vitamins C and E at 5 μM each. These results confirm, firstly, that catechol structure is very effective in terms of antioxidant activity and secondly, that linking an appropriate hydrophobic domain is a powerful strategy to synthesize effective antioxidants.Practical applications: Phenolic compounds (especially phenolic acids and flavonoids) are potent antioxidants that may play an important role as well in biological system (to prevent some risk factors associated with cancers, cardiovascular, and neurodegenerative diseases) as in formulated‐lipid dispersions. However, their activity is often limited by low solubility and stability in such systems. Lipophilization of phenolic compounds may increase their solubility in lipophilic matrices, conferring better antioxidant protection for food or non‐food application. In biological system, lipophilization may contribute to easier penetration of antioxidants through lipid bilayer of cell membranes, which can significantly increase their bioavailability. Thus, lipophilic phenolic derivatives provide a perspective of substances with maintained or improved biological properties for food, cosmetic, and pharmaceutical applications, playing an important role in the development of new drugs or food additives.A series of new model of lipophilized phenolic compound (1,2‐diacylglycerol rosmarinate, RDAG) were synthesized through a chemo‐enzymatic synthesis. In terms of antioxidant activity assessed in fibroblasts, all synthesized RDAG exhibited higher ROS inhibition level than free rosmarinic acid. RDAG with two lauryl chains (RDAG12) displayed the best antioxidant ability of the series, with higher activity than vitamins E and C. These results confirm that linking an appropriate hydrophobic domain is a powerful strategy to synthesize effective antioxidants.

The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic–Lipophilic Matrices

The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2h at pH1.2 and then 10h at pH6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p < 0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480min.

Review article: evolutionary advances in the delivery of aminosalicylates for the treatment of ulcerative colitis

Ulcerative colitis is a chronic and debilitating disease that involves inflammation of the colonic mucosa. Current therapies aim to reduce the symptom burden of ulcerative colitis and maintain disease quiescence. The standard first-line treatment for mild-to-moderate ulcerative colitis is 5-aminosalicylate therapy, which is available in oral and rectal (topical) formulations. While current 5-aminosalicylate formulations are effective in the majority of patients, they are associated with a number of limitations including inconvenient dosing regimens and poor patient acceptability, which may lead to non-compliance with prescribed therapy. A variety of improved delivery mechanisms have been developed in an effort to overcome these limitations. Micropellet formulations and high-dose tablets appear to offer comparable efficacy and tolerability to conventional formulations, although any benefit in terms of long-term patient compliance remains to be proven. Novel methods of delivery, such as those using a combination of hydrophilic and lipophilic matrices, designed to provide once-daily dosing in a high-strength tablet, may offer a significant improvement in the therapy of active and quiescent ulcerative colitis. This review examines the limitations of current 5-aminosalicylate formulations and reports on the evolution of novel oral formulations designed to overcome these limitations, maximize patient compliance during both induction and maintenance of quiescence, and optimize overall clinical outcomes.

Iron(II) sulfate release from drop-formed lipophilic matrices developed by special hot-melt technology

Iron(II) sulfate-containing lipophilic matrices were developed by a special hot-melt technology (melt solidification in drops), using stearin, white wax and their mixture as conventional bed materials. The special technology resulted in spherical particles which can be filled directly into capsules; these store iron as a depot and ensure a slow and uniform release, whereby the irritation of the gastric mucosa by the iron can be decreased. The rates of dissolution of the iron(II) sulfate from the various lipophilic matrices were different, but fundamentally low. Kinetic calculations demonstrated that the rate of dissolution of the iron(II) sulfate was of approximately zero kinetic order. The results of in vivo experiments on rabbits correlated well with the in vitro data. The plasma curves for the animals treated with the iron(II) sulfate preparations varied with the excipients in the depot products. The properties and ratio of the bed materials influenced the release of the iron(II) sulfate. In all probability, the release of the active agent can be regulated through the use of a melt of stearin and white wax in different ratios. The development products functioned as a sustained-release system and ensured elimination of the irritation of the gastric mucosa. At the same time, the results justified the applicability of the special hot-melt technology in the development of the solid dosage form.

Antioxidative potential of melanoidins isolated from a roasted glucose–glycine model

The antioxidative activity of the total water soluble fraction (sol A), high molecular weight (HMW; MW>12,400 Dalton), low molecular weight (LMW) and the insoluble fraction (IS) of a glucose–glycine model system roasted at 120°C was studied in hydrophilic solutions (PBS buffer, fruit juices; addition: 0.01–0.1%) at ambient temperature and lipophilic (coconut fat, triolein and corn oil; addition: 0.01–0.5%) matrices at 60°C and frying conditions at 200°C. The hydrophilic reducing power in the water-soluble fractions was evaluated with the ABTS [2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid)] method. Fat stability was determined by observing the development of the peroxide value and conjugated dienes. All fractions increased the hydrophilic reducing power in the water-soluble fractions as a matter of concentration with highest effects for the 0.1% enrichment. In PBS buffer the HMW was most effective, in fruit juices the IS. A slight antioxidative effect in fats was observed only for 0.5% IS and 0.5% sol A in corn oil. Neither in coconut fat at 200°C nor in triolein at 60°C Maillard reaction products (MRPs) were able to extend shelf life. The results performed describe MRPs as highly antioxidative in water-soluble but less effective in water-insoluble fractions.

Comparative Diffusion of Atrazine inside Aqueous or Organic Matrices and inside Plant Seedlings

Several different matrices (water, n-butanol, n-octanol, lecithin, waxes, and suber) were chosen to measure [14C]atrazine diffusion rate and evaluate the specific diffusion parameter of this molecule. A simple experimen tal device was conceived for this purpose and two methods of calculation, deduced from Fick's law, were established and compared. The same device was used for diffusion measurements inside corn seedling fragments, either dead or alive. In inert matrices, the highest diffusion parameter found for atrazine was obtained for water (2.6 ± 0.9) 10−10 m2 s−1. For more lipophilic matrices, the value of the specific parameter decreased markedly, reaching only (1.2 ± 1) 10−12 m2 s−1 for glycerides and (2.5 ± 2.4) 10−13 m2 s−1 for paraffin. For dead corn roots or coleoptile, the diffusion parameter was close to that in water: (3.7 ± 2.1) 10−10 m2 s−1 and (9.6 ± 4) 10−10 m2 s−1. In living material, the movement of 14C-labeled compounds was much lower: (7.4 ± 4.6) 10−11 m2 s−1 and (1.6 ± 1.5) 10−11 m2 s−1. This was explained by atrazine hydroxylation in the presence of benzoxazinones, leading to a derivative which was accumulated inside the vacuole.

New Cleanup Procedure for Determining Polychlorinated Dibenzo-P-Dioxins and Dibenzofurans in Lipophilic Matrices

A new cleanup procedure for determining polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in naturally occurring adipose matrices is suggested. The procedure can be used for analyzing butter, human and cow's milk, eggs, and meat. Quality of sample purification is better than that in the standard procedure, and the recovery of PCDD and PCDF internal standards is within the range 50–80%. The time it takes for sample preparation is shortened, and the consumption of solvents and sorbents is decreased. The FAS-MD activated carbon, which was especially prepared for the extraction of dioxins and related compounds, was used in this work.

Evaluation of mathematical models describing drug release from lipophilic matrices

Potassium chloride, as a highly watersoluble model drug was embedded into wax to produce sustained release dosage form. Samples were coated with different core:wall ratios to control the dissolution profile. The drug release from coated samples was tested by the rotating paddle method of USP and the dissolution data were analyzed assuming different kinetic models. Increasing the quantity of coating material may modify the drug liberation which was demonstrated by the correlation between proportion of the embedding material and mean dissolution time. It can be concluded that changing the quantity of embedding material both the dissolution rate and kinetic profile can be controlled.

Effects of the polymer matrix on an optical nitrate sensor based on a polarity-sensitive dye

A membrane responsive to nitrate has been developed; it is composed of a polymer matrix, an anion exchanger (tridodecylmethyl-ammonium chloride), and a polarity-sensitive dye (rhodamine B octadecyl ester perchlorate). On exposure to nitrate, its fluorescence intensity increases, while the wavelength of the excitation and emission maxima remain unchanged. The effect of the polymer matrix on the relative signal change, sensitivity and selectivity has been investigated. It is shown that the sensitivity and selectivity for nitrate over other anions strongly depends on the lipophilicity and polarity of the polymer: increasing lipophilicity results in both higher sensitivity and selectivity. The limit of detection (LOD) in the case of lipophilic matrices is of the order of 0.1 ppm nitrate, and highest signal changes are observed between 1 and 100 ppm. Hydrophilic matrices have an LOD of 1 ppm and are most sensitive to nitrate at levels between 10 and 1000 ppm. The selectivity factor of lipophilic matrices for nitrate over chloride is 200, whereas it is around 10 only in hydrophilic matrices. The optical signal of the sensor material is pH dependent and this dependence again is affected by the lipophilicity of the matrix. in general, lower lipophilicity increases the cross-sensitivity of the nitrate sensor to pH. As a result, the response of the sensor may be fine-tuned by the appropriate choice of the polymer material.

Mathematical models describing the drug release kinetics from pressure sensitive adhesive matrix

Several mathematical models for facilitating the interpretation of the release data cf lipophilic drugs from highly lipophilic matrices were proposed. Aminopyrine (AMP), ethinylestradiol (EE) and dipropylphthalate (DPP) were used as model drugs, and acrylic type pressure sensitive adhesive (PSA) was used as a model lipophilic matrix. Release experiments were performed using a diffusion cell at 37°C. AMP was completely released from the PSA, whereas only a fraction of EE and DPP loaded was released. There are usually several resistances involved in the diffusion of a drug through the matrix, such as interfacial transfer resistance (R) and transport resistance across the stagnant layer (H) during the drug release process; several equations containing above resistances were therefore developed in the Laplace dimension and used to interpret the obtained release data for the three drugs. Analysis of the results suggested that the stagrant layer could be neglected when using our type of diffusion cell and that the release data of the drugs from the PSA matrix could be interpreted by introducing the interfacial migration resistance and partition coefficient between the matrix and receiver solution into a Fick's diffusion equation.