The Effects of Backing Materials and Multilayered Systems on the Characteristics of Bioadhesive Buccal Patches

The effects of backing materials (ethylcellulose, polyvinylpyrrolidone and cellulose acetate mixture, and poly(ethylene-co-vinyl acetate) on the characteristics (hydration and adhesion) of newly developed bioadhesive patches for controlled drug delivery via the buccal mucosa were investigated. It was found that the swelling profiles of buccal patches were changed dramatically by the species and amount of the backing materials, and those changes could alter the drug release profile. The drug release profiles of single-layered and multilayered buccal patches were significantly different. It was demonstrated that the multiple-layer device could be used to modify the drug release for obtaining the ideal clinical pharmacokinetic release profile.     

An investigation of the chick chorioallantoic membrane as an alternative model to various biological tissues for permeation studies

Objectives The chick chorioallantoic membrane (CAM) was explored as a biological membrane for use in the study of drug permeation with a Franz diffusion cell. Methods The CAM was removed from fertilized chicken eggs of embryo age 9–18 days. The permeation profiles of nicotine through the fresh CAM were first obtained with a Franz diffusion cell. The permeation profiles of nicotine through frozen CAM, snake skin, pig skin, pig retina and pig buccal mucosa were also determined and compared with those of the fresh CAM. Key findings The permeability coefficient of the CAM varied with its age. The CAM at embryo age 13 was the most robust, showing the lowest standard error in permeability. It was thus chosen for comparative studies with snake skin, pig skin, retina and buccal mucosa. The CAM was found to be most similar to the buccal mucosa in terms of permeation profile and permeability coefficient values. Frozen CAM was also found to have a higher permeability coefficient than fresh CAM. The enhanced permeability was attributed to freezing, which affected the integrity of the CAM structure. Conclusions From the findings, CAM shows potential as an alternative to the pig buccal mucosa as an in‐vitro buccal model. The robustness of the CAM for drug permeation studies is affected by its age.     

Transmucosal delivery of domperidone from bilayered buccal patches: <Emphasis Type="Italic">In Vitro,Ex Vivo</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> characterization

Bilayered mucoadhesive buccal patches for systemic administration of domperidone (DOM), a dopamine-receptor (D₂) antagonist, were developed using hydroxy propyl methyl cellulose and PVPK30 as a primary layer and Eudragit RLPO and PEO as a secondary layer. Ex vivo drug permeation through porcine buccal membrane was performed. Bilayered buccal patches were developed by solvent casting technique and evaluated for in vitro drug release, moisture absorption, mechanical properties, surface pH, in vitro bioadhesion, in vivo residence time and ex vivo permeation of DOM through porcine buccal membrane from a bilayered buccal patch. Formulation DB4 was associated with 99.5% drug release with a higuchi model release profile and 53.9% of the drug had permeated in 6 h, with a flux of 0.492 mg/h/cm² through porcine buccal membrane. DB4 showed 5.58 N and 3.28 mJ peak detachment force and work of adhesion, respectively. The physicochemical interactions between DOM and the polymer were investigated by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) Spectroscopy. DSC and FTIR studies revealed no interaction between drug and polymer. Stability studies for optimized patch DB4 was carried out at 40°C/75% relative humidity. The formulations were found to be stable over a period of 3 months with respect to drug content, in vitro release and ex vivo permeation through porcine buccal membrane. The results indicate that suitable bilayered mucoadhesive buccal patches with desired permeability could be prepared.     

Development of mucoadhesive patches for buccal administration of carvedilol

A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution.     

多索茶碱脉冲控释微丸的研制

目的 研究多索茶碱脉冲控释微丸的制备工艺,并考察其释药性能。方法 以微晶纤维素为骨架材料采用挤出滚圆法制备载药丸芯,通过流化床包衣法分别覆上交联羧甲基纤维素钠作为溶胀层、乙基纤维素和羟丙甲纤维素作为控释层制备多索茶碱脉冲微丸,通过单因素考察筛选丸芯、溶胀层、控释层的处方组成对体外释药性能的影响。结果 以微晶纤维素、羧甲基淀粉钠和乳糖为添加剂可制得性能良好的高载药微丸。随着溶胀层厚度的增加,药物释放时滞变短,速率显著增加;随着控释层包衣厚度的增加,时滞延长,释药减慢;控释层中羟丙甲纤维素用量或分子量增加,时滞缩短;控释层中增塑剂用量增加,时滞延长。结论 所得包衣微丸具有良好的脉冲释药性能,有广阔的应用前景。     

Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies

Abstract

In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.     

Visualization and analysis of the release mechanism of shellac coated ascorbic acid pellets

Shellac coated sustained release ascorbic acid containing pellets were investigated using scanning electron microscopy in order to visualize the release mechanism and to establish a correlation to dissolution data. Scanning electron micrograph pictures revealed different drug release profiles of individual pellets. Single pellet dissolution measurements demonstrated that the release profile of the encapsulated dosage form, containing approximately 400 pellets per capsule, is a combination of different release profiles of all individual pellets. The release of ascorbic acid occurred only in some small spots on the surface area of the pellets and could be visualized by the reduction of silver ions from an aqueous silver nitrate solution. These spots could be identified as defects in the shellac sustained release film using scanning electron microscopy. In further trials, the dissolution rate of an individual pellet could be related to the number and dimension of holes in its membrane. In conclusion, the release is characterized by surface defects and scanning electron microscopy studies are a useful tool to get new information for a better understanding of the drug release.     

Pharmacokinetics and pharmacodynamics of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme inhibitor in spontaneously hypertensive rats

The pharmacokinetics and pharmacodynamics (PK/PD) of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in comparison with those of an osmotic pump in male spontaneously hypertensive rats (SHRs). A pellet was prepared from copolymer of -lactic acid and glycolic acid by the melt-pressing technique. Imidapril was released in vitro from the pellet at an approximately zero-order rate and the release profile was similar to that of the osmotic pump. Imidapril was administered subcutaneously via a pellet or an osmotic pump implanted under the skin in the back of SHRs. Plasma concentrations of imidaprilat as an active metabolite of imidapril, plasma ACE activity and systolic blood pressure (SBP) were determined periodically. The plasma concentration of imidaprilat during the administration of a pellet was maintained for 4 weeks, and the plasma concentration profile was close to that of the osmotic pump. Both groups of pellet and osmotic pump significantly inhibited plasma ACE activity and reduced SBP for 4 weeks, and these action profiles were similar in both groups. In addition, in vivo release profile of the pellet was close to the in vitro release profile, and the in vivo release profiles of the pellet and the osmotic pump were similar to each other. From these results, it was found that the PK/PD of a biodegradable pellet were close to those of the osmotic pump, and it was shown that the pellet may be a useful system to maintain the plasma concentration of imidaprilat for a long time.     

Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid

The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheological and turbidimetric analysis. Films containing 1 mg/cm2 of acyclovir and based on pure HCS and on HCS and PAA mixed in different ratios were prepared by casting technique. The films were subjected to hydration, rheological, mucoadhesion, drug release, "wash away," and permeation/penetration measurements. A commercial cream containing acyclovir and an aqueousacyclovir suspension were used as references. The addition of PAA to HCS produced a decrease in film hydration. Films based on HCS/PAA weight ratio close to interaction productstoichiometry were characterized by higher rigidity and better "wash away" properties with respect to the other films and the reference formulation. The worst mucoadhesive properties were shown by films based on mixing ratios close to interaction product stoichiometry. The addition of PAA to HCS produced a lowering in drug release profile. All the films examined promoted the permeation of acyclovir across porcine cheek epithelium when compared with acyclovir suspension and the commercial cream. The penetration enhancement properties were affected by the mixing ratio of the two polymers. The film based on 1/1.3 HCS/PAA weight ratio, besides possessing the best resilience properties on the mucosa, was also characterized by the highest permeation profile and, therefore, represents a promising formulation for buccal delivery of acyclovir.     

In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery

In this work the enhancing effect of cyclodextrins on the buccal permeation of a hydrophobic model drug, omeprazole was studied. First, the influence of the complexation with cyclodextrins in the absence and in the presence of an alkali agent, l-arginine, on the drug stability was checked at neutral conditions since omeprazole alone is only stable in basic conditions. In vitro transbuccal permeation of omeprazole non-complexed and complexed with β- and methyl-β-cyclodextrin and in presence of l-arginine was examined using freshly obtained porcine buccal mucosa. Tissue viability after incubation with sample solutions was assessed using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) biochemical assay and histological evaluation. The toxicity of the sample solutions on buccal mucosa was evaluated by measuring lactate dehydrogenase activity. The present results show that complexation with cyclodextrins increases drug stability at neutral conditions; furthermore, l-arginine contributed to higher drug stability. Permeation studies indicate an increase on drug permeation in complexed form of 1.1- and 1.7-fold for β-cyclodextrin and methyl-β-cyclodextrin, respectively. The presence of l-arginine increases drug permeation 1.4-fold in omeprazole complexed with β-cyclodextrin and 2.4-fold in the inclusion complex formed with methyl-β-cyclodextrin. The cell viability of the buccal mucosa after a 3 h incubation period, with all sample solutions, remained around 70% and lactate dehydrogenase assay showed that studied cyclodextrins, even in the presence of an alkali agent are not cytotoxic for porcine buccal mucosa. Histological evaluation of the tissue demonstrated that the buccal epithelium remains viable after 3 h of incubation with sample solutions.     

Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique

The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.     

Release Behaviour of Single Pellets and Internal Fine 3D Structural Features Co-define the In Vitro Drug Release Profile

Multi-pellet formulations are advantageous for the controlled release of drugs over single-unit dosage forms. To understand the diffusion controlled drug release mechanism, the pellet structure and drug release from a single pellet (not at dose level) were studied using synchrotron radiation X-ray computed microtomography (SR-μCT) and a sensitive LC/MS/MS method. The purpose of this article is to introduce a powerful, non-invasive and quantitative technique for studying individual pellet microstructures and to investigate the relationship between the microstructure and drug release from single pellets. The data from the single pellet dissolution measurements demonstrated that the release profile of capsules containing approximately 1,000 pellets per unit dose was the summation of the release profiles of the individual pellets. The release profiles of single tamsulosin hydrochloride (TSH) pellets formed three groups when a cluster analysis was performed, and the dissolution rate of the individual pellets correlated well with the combined effects of the drug loading, volume and surface area of the pellets (R² = 0.9429). In addition, the void microstructures within the pellet were critical during drug release. Therefore, SR-μCT is a powerful tool for quantitatively elucidating the three-dimensional microstructure of the individual pellets; because the microstructure controls drug release, it is an important parameter in the quality control of multi-pellet formulations.KEY WORDS: microstructure, release kinetics, single pellet, synchrotron radiation X-ray computed microtomography     

Transbuccal permeation of a nucleoside analog, dideoxycytidine: effects of menthol as a permeation enhancer

The use of a safe and effective permeation enhancer is paramount to the success of a buccal drug delivery system intended for systemic drug absorption. The enhancing effects of menthol (dissolved in an aqueous buffer in the absence of co-enhancers) on buccal permeation of a model hydrophilic nucleoside analog, dideoxycytidine (ddC), were investigated. In vitro transbuccal permeation of ddC was examined using freshly obtained porcine buccal mucosa. The experiments were carried out in side-bi-side flow through diffusion cells. Permeation enhancement studies were performed with varying concentrations of l-menthol dissolved in Krebs buffer solutions containing ddC. Partition coefficient experiments were carried out to probe into the mechanism of permeation enhancing properties of l-menthol and DSC studies were conducted to determine if there is a eutectic formation between ddC and l-menthol at various concentrations. Permeation of ddC increased significantly (P<0.05) in the presence of l-menthol independent of the concentration of the terpene. The apparent 1-octanol/buffer partition coefficient (log K(p)) of ddC was significantly (P<0.05) increased in presence of l-menthol and was also independent of the enhancer concentration. However, the tissue/buffer partition coefficient (log K'(p)) data showed a concentration dependent increase of log K'(p) in presence of l-menthol. Since log K'(p) is a measure of drug binding to the tissue in addition to drug partitioning, binding of ddC to the buccal tissue may provide an explanation for the concentration dependent increase in these values.     

Development of buccal drug delivery systems based on a thiolated polymer

The purpose of the present study was to investigate the benefit of thiolated polymers (thiomers) for the development of buccal drug delivery systems. L-Cysteine was thereby covalently attached to polycarbophil (PCP) mediated by a carbodiimide. The resulting conjugate displayed 140.5+/-8.4 microM thiol groups per gram polymer. Disintegration studies were carried out with tablets based on unmodified polymer and conjugated polymer, respectively. Due to the formation of disulfide bonds within the thiolated polymer, the stability of matrix-tablets based on this polymer was strongly improved. Additionally tensile studies were carried out, which were in good correlation with further results obtained by mucoadhesion studies, using the rotating cylinder method. These results showed that tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding control. Moreover, the enzyme inhibitory properties of polymers were evaluated as well. Thiolated PCP increased the stability of the synthetic substrate for aminopeptidase N-leu-p-nitroanilide (N-leu-pNA) and the model drug leucin-enkephalin (leu-enkephalin) against enzymatic degradation on buccal mucosa. Due to the use of thiolated polymers also a controlled drug release for leu-enkephalin was guaranteed over a time period for more than 24 h. Results of the present studies suggest that thiolated polymers represent a very useful tool for buccal delivery of peptide drugs.     

Indomethacin sustained release pellets prepared by extrusion-spheronization

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10 % w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20 %) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10 % has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.     

Use of kappa-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. I. Influence of type and fraction of filler.

Microcrystalline cellulose (MCC) is commonly used as an excipient in extrusion/spheronisation process. However, MCC has several disadvantages as lack of disintegration and drug adsorption. Therefore, kappa-carrageenan was investigated to substitute MCC in pelletising processes. Formulations with 20% of pelletisation aid (kappa-carrageenan or MCC) and acetaminophen as a model drug have been produced. Different fillers (lactose, mannitol, maize starch and dicalciumphosphate dihydrate) at fractions of 0, 20, 40 and 80% were evaluated and the properties of the resulted pellets were determined (e.g. yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength and release profile). kappa-Carrageenan has proven to be a suitable substitute as pellets with sufficient quality were produced. The pellet batches of different formulations were characterised by high yield, spherical pellet shape and narrow pellet size distribution. The distinguished behaviour between kappa-carrageenan and MCC pellets was the lower tensile strength and the faster release of kappa-carrageenan pellets. For the various types and fractions of fillers only minor effects to the pelletisation process and pellet properties were noticed. From the practical view these effects are neglectable indicating a robust formulation and process.     

Advances in buccal drug delivery

The buccal route offers an attractive alternative for systemic drug delivery of drugs because of better patient compliance, ease of dosage form removal in emergencies, robustness, and good accessibility. Use of buccal mucosa for drug absorption was first attempted by Sobrero in 1847, and since then much research was done to deliver drugs through this route. Today, research is more focused on the development of suitable delivery devices, permeation enhancement, and buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. In this review, the anatomy and physiology of buccal mucosa, followed by discussion of recent literature on the buccal permeation enhancement, and pathways of enhancement for various molecules are detailed. In addition, bioadhesion theories from historic perspective and current status are discussed. The various dosage forms on the market and in different stages of development are also reviewed.     

TR146 cells grown on filters as a model of human buccal epithelium: III. Permeability enhancement by different pH values, different osmolality values, and bile salts.

The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P(app)) of the hydrophilic marker mannitol due to exposure to solutions with pH values or osmolality values different from the physiological values was studied. As in studies with solutions of either taurocholate (TC), glycocholate (GC) or glycodeoxycholate (GDC) the results were compared to the increase in P(app) of mannitol obtained in analog studies using porcine buccal mucosa in an Ussing chamber. The effect of the exposure on the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa was measured, and the degree of protein leakage due to GC exposure was investigated in the TR146 cell culture model. The porcine buccal mucosa was approximately ten times less permeable to mannitol than the TR146 cell culture model. The P(app)TC. Increased P(app) values correlated with a decrease in the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa. GC was shown to induce concentration dependent protein leakage in the TR146 cell culture but only from the site of application, and the results indicate that duration of exposure further than 120 min was of minor importance. The present results indicate that the TR146 cell culture model may be a suitable in vitro model for efficacy studies and mechanistic studies of enhancers with potential use in human buccal drug delivery.     

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m^?1 S^?2 and more than 2.5 kg/3 cm², respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.     

Dissolution profile of novel composite pellet cores based on different ratios of microcrystalline cellulose and isomalt

There is a growing interest towards the application of inert cores as starting materials for pharmaceutical pellet manufacturing. They serve as alternatives to develop and adapt a relatively simple manufacturing technology compared with an extrusion/spheronisation process. The major objective of this study was to investigate the effect of the compositions of core materials on the drug release profile. Pure microcrystalline cellulose (MCC), isomalt and different types of novel composite MCC-isomalt cores were layered with model drug (sodium diclofenac) and were coated with acrylic polymer. The effect of the osmolality in the gastrointestinal tract was simulated using glucose as osmotically active agent during in vitro dissolution tests. The results demonstrated the dependence of drug dissolution profile on the ratio of MCC and isomalt in the core and the influence of osmotic properties of the dissolution medium. Isomalt used in the composite core was able to decrease the vulnerability of the dissolution kinetics to the changes in the osmotic environment.