International Journal of Pharmaceutics (v.364, #1)

The crystallization kinetics of hemipenta hydrate risedronate monosodium (RS) were investigated in cooling mode. The solubility, induction time, mechanism of nucleation and crystal growth in the crystallization of hemipenta hydrate RS in water as a solvent were determined by the in situ measurement using focused beam reflectance measurement (FBRM). The relationship between induction time and the supersaturation was obtained for understanding mechanism of nucleation. The nucleation mechanism including homogeneous and heterogeneous nucleation was grasped with respect to the supersaturation. From the results of nucleation experiments, the interfacial tension of hemipenta hydrate RS was determined. Furthermore, the kinetics of crystal growth was also obtained. The crystal growth of hemipenta hydrate RS was controlled by the combination of one and two-dimensional growth mechanisms.
Keywords: Hydrate formation; Kinetics; Crystallization; Risedronate;

In the present investigations new drug delivery systems have been developed, which are controlled by a computer and a high frequency energy transmission system. The capsules consist of a drug reservoir, a high frequency receiver, a gas generating section and a piston to pump a drug solution or drug suspension out of the reservoir. Mechanical energy is generated inside the capsule through electrolysis, if a 27 MHz high frequency field is in resonance with the receiver inside the capsule. Two different miniaturised oscillatory circuits were constructed, which act as the receivers in the capsules. Tramadol was used in release experiments as a model drug. Delayed and pulsed release profiles were obtained. A computer-controlled system was constructed, in which the programmed release profiles are compared with the actual release of the drug.
Keywords: High frequency energy transmission system; Delayed drug release; Pulsed release; Gas generating reactor; Tramadol;

Optimization of ibuprofen gel formulations using experimental design technique for enhanced transdermal penetration by Yun-Seok Rhee; Si-Young Chang; Chun-Woong Park; Sang-Cheol Chi; Eun-Seok Park (14-20).
The aims of this study were to develop a transdermal gel formulation for ibuprofen using experimental design techniques and to evaluate its pharmacokinetic properties. The three factors chosen for factorial design were the concentrations of drug, polyoxyethylene(5)cetyl/oleyl ether and ethanol and the levels of each factor were low, medium and high. Skin permeation rates and lag times of ibuprofen were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of ibuprofen significantly increased in proportion to the drug concentration, but significantly decreased in proportion to POE(5)cetyl/oleyl ether concentration. Ethanol concentration was inversely proportional to the lag time. The pharmacokinetic properties of the optimized formulation were compared with those of two marketed products in rats. The relative bioavailability of ibuprofen gel compared to the two marketed products was 228.8% and 181.0%. In conclusion, a transdermal ibuprofen gel was formulated successfully using the technique of experimental design and these results helped in finding the optimum formulation for transdermal drug release.
Keywords: Ibuprofen; Gel; Transdermal; Experimental design; Pharmacokinetic;

A novel riboflavin gastro-mucoadhesive delivery system based on ion-exchange fiber by Huimin Yao; Lu Xu; Fei Han; Xin Che; Yang Dong; Min Wei; Jiao Guan; Xiaolei Shi; Sanming Li (21-26).
A novel gastro-mucoadhesive delivery system based on ion-exchange fiber has been developed. Rriboflavin-5′-phosphate sodium salt (RF5P), which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. A modified dissolution system, which can also be called ‘flow through diffusion cell’ (FTDC), was used to study the drug release from the drug fibers. Gastrointestinal transit studies of the RF5P fiber complexes in rats and gamma imaging study in volunteer was carried out to evaluate the gastro-retentive behavior of the fiber. The pharmacokinetic profile and parameters of riboflavin via analysis of urinary excretion of riboflavin on man were measured. Study on rat and man provide evidence for the validity of the hypothesis that the drug fiber provided good mucoadhesive properties in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.
Keywords: Gastro-mucoadhesive dosage form; Riboflavin; Ion-exchange fiber; Modified dissolution system; Flow through diffusion cell; Pharmacokinetic;

The purpose of this study was to investigate the plasma pharmacokinetics and brain uptake of a lipophilic benzodiazepine anticonvulsant, diazepam in New Zealand white rabbits and Sprague–Dawley rats to evaluate the possible absorption pathways after intravenous and intranasal administration. The intranasal formulation was prepared by dissolving DZ and 1% sodium glycocholate into microemulsion system composed of 15% ethyl laurate, 25% Labrasol®, 37.5% Transcutol®P, 12.5% ethanol, and 10% water. Diazepam was administered intravenously (1 mg/kg) or intranasally (2 mg/kg) to rats and rabbits. Drug concentrations in the plasma and six different regions of the brain tissues, i.e., olfactory bulb, olfactory tract, anterior, middle, and posterior segments of cerebrum and cerebellum were analyzed by LC/MS method after solid phase extraction. After IN administration, DZ was rapidly absorbed into the systemic circulation, and readily and homogenously distributed into the different regions of brain tissues with a t max of 5 and 10 min in rats and rabbits, respectively. The bioavailability of DZ in rat plasma (68.4%) and brain (67.7%) were 32–47% higher than those observed in rabbit plasma (51.6%) and brain (45.9%). The AUCbrain/AUCplasma ratios in rabbits after IN administration (3.77 ± 0.17) were slightly lower than from IV administration (4.23 ± 0.08). However, in rats the AUCbrain/AUCplasma ratios after IV (3.03 ± 0.07) and IN (3.00 ± 0.32) administration were nearly identical. The plasma pharmacokinetic and distribution studies in the two animal models clearly showed that lipophilic DZ molecules reached the brain predominantly from the blood by crossing the blood–brain barrier after IN administration with no significant direct nose-to-brain transport via olfactory epithelium.
Keywords: Diazepam; Intranasal absorption; Pharmacokinetics; Brain distribution; Status epilepticus;

Genistein, daidzein, and glycitein are soy isoflavones. These compounds can be used to protect the skin from oxidative stress induced by UVB radiation. To this end, the feasibility of skin absorption of soy isoflavones was evaluated in the present study. As assayed by flow cytometry, UVB-induced H2O2 production in keratinocytes was inhibited by genistein and daidzein, confirming that these two compounds can act as free radical scavengers when keratinocytes are photodamaged. Glycitein showed no protective activity against photodamage. The effects of vehicles on the in vitro topical delivery from saturated solutions such as aqueous buffers and soybean oil were investigated. The isoflavones in a non-ionized form (pH 6) showed higher skin deposition compared to the ionized form (pH 10.8). Soybean oil reduced the isoflavone amount retained in the skin, especially for genistein. Genistein generally exhibited greater skin absorption than did daidzein. However, daidzein permeation was enhanced when an aglycone mixture was used as the active ingredient. An eutectic effect was proposed as the enhancing mechanism. In vivo skin deposition showed a linear correlation with the in vitro results. The safety profiles suggested no or only negligible stratum corneum disruption and skin erythema by topical application of soy isoflavones. It was concluded that topical delivery may serve as a potent route for soy isoflavones against photoaging and photodamage.
Keywords: Soy isoflavones; Genistein; Daidzein; Skin; Topical delivery; UVB;

Kinetics of solvent extraction/evaporation process for PLGA microparticle fabrication by Hajime Katou; Anne Julia Wandrey; Bruno Gander (45-53).
Organic solvent extraction/evaporation from an o/w-dispersion has been widely used for the fabrication of PLGA microparticles. The purpose of this work was to elucidate the kinetics of the solvent extraction/evaporation process. A mathematical diffusion model was developed and applied to predict the duration of the solvent extraction. As the diffusion coefficient, D p, plays a major role in the modeled process, a new and experimentally simple method for estimating D p was developed. Both the experimental method and the mathematical model were validated through PLGA microparticle fabrication experiments. For microparticles of mode diameters of 2 and 20 μm, the solvent was extracted in approximately 10 s. Sufficient hardening of the microparticles required, however, the evaporation of solvent from the extraction phase. Residual solvent in extraction phase exerted a strong effect on the morphology of the final product as demonstrated by scanning electron microscopy. Only if most solvent was removed from the aqueous extraction phase, a powdery product of individual microparticles was obtained. At residual organic solvent concentration of above 0.2% in the extraction phase, the microparticles strongly aggregated during collection on a membrane filter and final drying. The presented methods may be useful for better controlling microparticle fabrication processes by solvent extraction/evaporation.
Keywords: Solvent extraction; Solvent diffusion; Mathematical model; PLGA; Microparticle fabrication;

Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa by J. Goole; B. Van Gansbeke; G. Pilcer; Ph. Deleuze; D. Blocklet; S. Goldman; M. Pandolfo; F. Vanderbist; K. Amighi (54-63).
In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers. Two concepts of sustained-release floating minitablets – Levo-Form 1 (matrix) and 2 (coated) – were evaluated and compared to the marketed product Prolopa® HBS 125. All the floating forms were radiolabelled with 111In in order to evaluate their gastric residence time using γ-scintigraphy. It was shown that the three formulations offered almost the same mean gastric residence time, which was about 240 min. Prolopa® HBS 125 and Levo-Form 2 presented intragastric disintegration, which can lead to a more pronounced “peak & valley” effect on the plasma concentration–time profile of levodopa. In contrast, the plasma concentration–time profile of levodopa following the administration of Levo-Form 1 was more evenly distributed. Moreover, Levo-Form 1 provided the lowest variations between men and women in terms of AUC and C max values. Finally, when the same amount of inhibitors of extracerebral dopa decarboxylase – carbidopa and benserazide – had been administrated, the mean AUC, C max and T max values obtained for benserazide were lower than those obtained for carbidopa.
Keywords: Clinical study; Gamma scintigraphy; Pharmacokinetics; Minitablets; Floating; Sustained-release; Levodopa; Carbidopa;

During the last 10–15 years, the formulation of drugs as nanocrystals has rapidly evolved into a mature drug delivery strategy, with currently five products on the market. The major characteristic of these systems is the rapid dissolution velocity, enabling bioavailability enhancement after oral administration. This mini-review focuses on recent advances with respect to three topics considering drug nanocrystals. The first topic is nanosuspension stabilization. A current literature status is provided and special attention is given to studies attempting to extend our physicochemical understanding of the underlying principles. The second part describes recent advances on miniaturization of nanosuspension production, to enable formulation screening during preclinical development. Finally, literature available on further nanosuspensions solidification is discussed, focussing on the maintenance of the preservation of the rapid dissolution properties of the nanocrystals after further downstream processing.
Keywords: Nanosuspension; Stabilization; Miniaturization; Drying; Solids;

Cyclosporine A loaded SLNs: Evaluation of cellular uptake and corneal cytotoxicity by Evren H. Gokce; Giuseppina Sandri; M. Cristina Bonferoni; Silvia Rossi; Franca Ferrari; Tamer Güneri; Carla Caramella (76-86).
Cyclosporine A (CsA) loaded solid lipid nanoparticles (SLNs) for topical ophthalmic applications were prepared by high shear homogenization and ultrasound method using Compritol 888 ATO, Poloxamer 188 and Tween 80, to investigate the cellular uptake of rabbit corneal epithelial cells (RCE) and to evaluate the cytotoxicity. The size of the optimized formulation was 225.9 ± 5.5 nm with a polydispersity index of 0.253 ± 0.05. The zeta potential and entrapment efficiency was detected as −16.9 ± 0.7 mV and 95.6%, respectively. The CsA release was found to be enzyme (lipase/co-lipase complex) dependent. SLNs were sterilized at 110 and 121 °C. The cytotoxicity was evaluated in vitro by means of RCE cells and was higher at 121 °C sterilization temperature, probably due to a supposed leakage of Tween 80 following lipid re-crystallization. The permeation and penetration of CsA across/into the corneal cells were evaluated using in vitro and ex vivo experiments. The cellular uptake was investigated by replacing CsA with the fluorescent dye Rhodamine B. The penetration enhancement properties were supported by confocal laser scanning microscopy analysis. The internalization of SLNs in cornea and in RCE cell lines was confirmed, pointing out the possibility of CsA targeting to the cornea.
Keywords: Solid lipid nanoparticles; Cyclosporine A; Ophthalmic; Cytotoxicity; Penetration; Cellular uptake;

We have successfully fabricated a dual drug release electrospun scaffold containing an anesthetic, lidocaine, and an antibiotic, mupirocin. Two drugs with different lipophilicities were electrospun from a poly-l-lactic acid (PLLA) solution with a dual spinneret electrospinning apparatus into a single scaffold. The release of the drugs from the scaffold showed different profiles for the two drugs. Lidocaine hydrochloride exhibited an initial burst release (80% release within an hour) followed by a plateau after the first few hours. Mupirocin exhibited only a 5% release in the first hour before experiencing a more sustained release to provide antibacterial action for over 72 h. For comparative purposes, both drugs were spun from a single spinneret and evaluated to determine their release profiles. The scaffold maintained its antibiotic activity throughout the processes of electrospinning and gas sterilization and supported cell viability. It has been reported in the literature that interactions between polymer and drug are known to govern the pattern of drug release from electrospun scaffolds. Here, it was found that the presence of the two drugs in the same polymer matrix altered the release kinetics of at least one drug. Based on the release profiles obtained, the dual spinneret technique was the preferred method of scaffold fabrication over the single spinneret technique to obtain a prototype wound healing device.
Keywords: Electrospinning; Wound; Antibiotic; Anesthetic; Lidocaine; Muciprocin; PLLA;

Amine-functionalized gold nanoparticles as non-cytotoxic and efficient intracellular siRNA delivery carriers by Soo Hyeon Lee; Ki Hyun Bae; Sun Hwa Kim; Kyu Ri Lee; Tae Gwan Park (94-101).
Gold nanoparticles chemically modified with primary amine groups were developed as intracellular delivery vehicles for therapeutic small interfering RNA (siRNA). The positively charged gold nanoparticles could form stable polyelectrolyte complexes through electrostatic interactions with negatively charged siRNA–polyethylene glycol (PEG) conjugates having a cleavable di-sulfide linkage under reductive cytosol condition. The resultant core/shell type polyelectrolyte complexes surrounded by a protective PEG shell layer had a well-dispersed nanostructure with a hydrodynamic diameter of 96.3 ± 25.9 nm, as determined by dynamic light scattering and transmission electron microscopy. Confocal laser scanning microscopy revealed that the nanosized polyelectrolyte complexes were efficiently internalized in human prostate carcinoma cells, and thus enhanced intracellular uptake of siRNA. Furthermore, the siRNA/gold complexes significantly inhibited the expression of a target gene within the cells without showing severe cytotoxicity. The current study demonstrated that positively charged gold nanoparticles could be potentially applied for intracellular delivery of siRNA.
Keywords: Gold nanoparticles; Small interfering RNA (siRNA); Poly(ethylene glycol); Polyelectrolyte complex; Gene delivery;

Semi-permeable nanocapsules of konjac glucomannan–chitosan for enzyme immobilization by Rui Wang; Bing Xia; Bang-Jing Li; Shu-Lin Peng; Li-Sheng Ding; Sheng Zhang (102-107).
Carboxymethyl konjac glucomannan–chitosan (CKGM–CS) nanocapsules, spontaneously prepared under very mild conditions by electrostatic complexation, were used for immobilizing l-asparaginase. The matrix has semi-permeability to allow the substrate and product to pass through and to keep l-asparaginase in the matrix to prevent leaking. The cell-like hydrogel matrix was prepared in aqueous system without organic solvents and reagents. The process of the preparation does not denature the enzyme and the activity of the immobilized and native enzyme is very similar. The activity, stability, and characters of the enzyme-loaded nanocapsules were studied. The results indicated the immobilized enzyme has better stability and activity in contrast to the native enzyme. These studies may supply a new material for the immobilization of pH and temperature-sensitive enzyme.
Keywords: Carboxymethyl konjac glucomannan; Chitosan; Nanocapsule; l-Asparaginase; Immobilization; Semi-permeability;

The aim of this work was to investigate lipid-based dried powders as transfection competent carriers capable of promoting the expression of therapeutic genes. The lipid-based vectors were prepared by combining different cationic lipids 1,2-dioleoyl-3-trimethylammoniumpropane chloride (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 3β(N(N′,N-dimethylaminoethane) carbamoyl) cholesterol hydrochloride (DC-Chol) or by mixing of anionic lipids (1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol sodium salt (DMPG) and chitosan salts. Spray drying of the formulations was performed using carbohydrates as thermoprotectant excipients and some aminoacids as aerosolisation enhancers. Both the lipidic vectors and the dried powders were characterized for morphology, size, zeta potential (Z-potential) and a yield of the process. Agarose gel electrophoresis was used to examine the structural integrity of dehydrated plasmid DNA (pDNA). The biological functionality of the powders was quantified using the in vitro cell transfection. Among the several lipids and lipid–polymer mixtures tested, the best-selected formulations had spherical shape, narrow size distribution (mean diameter < 220 nm, P.I. < 0.250), a positive zeta-potential (>25 mV) with a good yield of the process (>65%). The set-up spray drying parameters allowed to obtain good yield of the process (>50%) and spherically shaped particles with the volume-weighted mean diameter (d[4,3]) < 6 μm in the respirable range. The set-up conditions for the preparation of the lipid dried powders did not adversely affect the structural integrity of the encapsulated pDNA. The powders kept a good transfection efficiency as compared to the fresh colloidal formulations. Lipid-based spray dried powders allowed the development of stable and viable formulations for respiratory gene delivery. In vitro dispersibility and deposition studies are in progress to determine the aerosolisation properties of the powders.
Keywords: Cationic lipids; Chitosan; LPD complexes; Spray drying; Ex vivo transfection; Respiratory gene delivery;

The objective of the present investigation was to explore the potential of nanostructured lipid carriers (NLC) for the intravenous delivery of artemether (ARM), a poorly water-soluble antimalarial agent. The NLC of ARM (Nanoject) were formulated by employing a microemulsion template technique. The NLC were evaluated for particle size, encapsulation efficiency, in vitro drug release and in vitro hemolysis. The antimalarial activity of the Nanoject and conventional ARM injectable formulation was evaluated in Plasmodium berghei infected mice. The average particle size of Nanoject was 63 ± 28 nm and the encapsulation efficiency was found to be 30 ± 2%. The Nanoject released ARM in a sustained manner. In vitro haemolytic studies showed that Nanoject had lower haemolytic potential (∼13%) as compared to all the components when studied individually. Nanoject showed significantly higher (P  < 0.005) antimalarial activity as compared to the marketed injectable formulation. The antimalarial activity of Nanoject lasted for a longer duration (more than 20 days) indicating that Nanoject may be long-circulating in vivo. Nanoject showed significantly higher survival rate (60%) even after 31 days as compared to marketed formulation which showed 0% survival (100% mortality). This clearly indicates that Nanoject offers several advantages over the currently marketed oily intramuscular formulation (Larither®).
Keywords: Malaria; Artemether; Intravenous; Nanostructured lipid carriers; Antimalarial activity;

Methylated N-(4-pyridinylmethyl) chitosan as a novel effective safe gene carrier by Praneet Opanasopit; Warayuth Sajomsang; Uracha Ruktanonchai; Varissaporn Mayen; Theerasak Rojanarata; Tanasait Ngawhirunpat (127-134).
The objective of this study was to study the transfection efficiency of quaternized N-(4-pyridinylmethyl) chitosan; TM-Py-CS, using the pDNA encoding green fluorescent protein (pEGFP-C2) on human hepatoma cell lines (Huh 7 cells). The factors affecting the transfection efficiency, e.g. degree of quaternization (DQ), the extent of N-pyridinylmethyl substitution (ES) and weight ratio, have been investigated. The results revealed that TM-Py-CS was able to condense with pDNA. Illustrated by agarose gel electrophoresis, complete complexes of TM69Py62CS/DNA were formed at weight ratio above 1.1, whereas those of TM53Py40CS/DNA and TM52Py13CS/DNA were above 1.8 and 8, respectively. TM69Py62CS showed superior transfection efficiency to TM53Py40CS, TM52Py13CS, TM65CS and TM43CS at all weight ratios tested. The highest transfection efficiency of TM69Py62CS/DNA complexes was found at weight ratio of 4. The results indicated that the improved gene transfection was possibly due to 4-pyridinylmethyl substitution on CS which promoted the interaction and condensation with DNA as well as N-quaternization which increased CS water solubility. In cytotoxicity studies, high concentration of TM-Py-CS and TM-CS could decrease the Huh 7 cell viability. In conclusion, this novel CS derivative, TM69Py62CS, showed promising potential as a gene carrier by efficient DNA condensation and mediated higher level of gene transfection.
Keywords: Methylated N-(4-pyridinylmethyl) chitosan; Gene delivery; Huh 7 cells; Transfection efficiency;

The purpose of this study was to investigate solid lipid nanoparticles (SLN) hydrogel for transdermal iontophoretic drug delivery. Triamcinolone acetonide acetate (TAA), a glucocorticoids compound, was employed as the model drug. SLN containing the drug triamcinolone acetonide acetate (TAA-SLN) and their carbopol gel with stable physicochemical properties were prepared. The use of TAA-SLN carbopol gel as a vehicle for the transdermal iontophoretic delivery of TAA was evaluated in vitro using horizontal diffusion cells fitted with porcine ear skin. We found that the TAA-SLN gel possessed good stability, rheological properties, and high electric conductance. Transdermal penetration of TAA from TAA-SLN gel cross the skin tissue was significantly enhanced by iontophoresis. The enhancement of the cumulative penetration amount and the steady-state penetration flux of the penetrated drug were related to the particle size of TAA-SLN and the characteristics of the applied pulse electric current, such as density, frequency, and on/off interval ratio. These results indicated that SLN carbopol gel could be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.
Keywords: Transdermal drug delivery; Iontophoresis; Solid lipid nanoparticles; Carbopol gel; Triamcinolone acetonide acetate;

PAMAM G4 dendrimers lower high glucose but do not improve reduced survival in diabetic rats by Magdalena Labieniec; Olga Ulicna; Olga Vancova; Rafal Glowacki; Katarina Sebekova; Edward Bald; Teresa Gabryelak; Cezary Watala (142-149).
For nearly a decade poly(amidoamine) (PAMAM) dendrimers G4 were claimed unnegligible cytotoxic agents. Here we monitored whether in vivo cytotoxic effect of PAMAM G4 (0.5 μmol kg−1  day−1) may be compromised by its ameliorating effect on severe hyperglycaemia in chronic streptozotocin-diabetic Wistar rats. PAMAM G4 significantly reduced the 60-day overall survival in long-term experimental diabetes: treated animals were 6.7 times more likely to die than control animals (p  < 0.025). PAMAM G4 significantly reduced numerous biochemical parameters in blood, including glucose, glycated haemoglobin or protein oxidation, cholesterol and triglycerides, but apparently unchanged plasma insulin peptide C. Terminal blood glucose in PAMAM-treated animals was significantly higher in survivors, pointing to the possible preventive role of glycation in reducing of PAMAM G4 cytotoxicity.Our results provide the first in vivo evidence that PAMAM G4 is able to lower plasma glucose and suppress long-term markers of diabetic hyperglycaemia. Nevertheless, this beneficial influence cannot override PAMAM G4 cytotoxic effects in the increased mortality of streptozotocin-diabetic rats.
Keywords: PAMAM G4; Survival; Streptozotocin diabetes; Hyperglycaemia; Protein glycation;

Novel wound models for characterizing ibuprofen release from foam dressings by Bente Steffansen; Sofie P.K. Herping (150-155).
The purpose of the present study was to design and characterize low exudate level wound (LEW) and high exudate level wound (HEW) in vitro models by means of investigating therapeutic substance release from exudate-absorbing formulations. Biatain®Ibu foam dressing was used to characterize in vitro release of ibuprofen within the models and also for in vitroin vivo correlation (IVIVC) studies. Ibuprofen release was described by zero order rate constants of 0.0147 for 1 day and 0.0038 mg/cm2  h for 3 days in HEW and LEW models, respectively. The release is suggested to be controlled by ibuprofen diffusion from the dressing in the HEW model, whereas fluid absorption is rate-limiting in the LEW model. Ibuprofen release, from Biatain®Ibu foam dressings in vivo, is within the same ranges as in vitro. Thus, it is suggested that, depending on the level of exudate, the in vivo release of ibuprofen depends on ibuprofen diffusion from and absorption of exudates to the dressings. Consequently, both the HEW and LEW in vitro models should be applied in order to fully characterize ibuprofen release from Biatain®Ibu foam dressings. Future studies may show whether these in vitro models can be used to characterize therapeutic substance release from exudate-absorbing formulations in general.
Keywords: In vitro wound exudate level models; Ibuprofen; Wound foam dressing; Exudate level-controlled release; IVIVC;

Noticeboard (156).