pH-Sensitive Polymer Blends Used as Coating Materials to Control Drug Release from Spherical Beads: Elucidation of the Underlying Mass Transport Mechanisms

Purpose To elucidate the drug release mechanisms from pellets coated with pH-sensitive polymer blends.Methods Verapamil hydrochloride-loaded beads were coated with various blends of a water-insoluble and an enteric polymer, ethylcellulose:Eudragit L and Eudragit NE:Eudragit L, respectively. Both experimental and theoretical techniques were used to characterize the systems before and upon exposure to 0.1 M HCl and phosphate buffer (pH 7.4).Results Using analytical solutions of Fick’s second law of diffusion, optical and scanning electron microscopy, and mechanical and gravimetric analysis, new insight into the underlying drug release mechanisms could be gained. More importantly, the latter can be effectively altered by varying the type of polymer blend and blend ratio. For example, at low pH drug release is primarily controlled by diffusion through the intact film coatings in Eudragit NE:Eudragit L blends, whereas crack formation is of major importance in ethylcellulose:Eudragit L-coated systems. At high pH, the (partial) leaching of the enteric polymer out of the coatings plays an important role. In all cases, the observed drug release profiles could be explained based on the occurring mass transport processes.Conclusions The obtained new knowledge can be used to effectively adjust desired drug release mechanisms and, thus, release patterns.     

Polymer Blends Used for the Coating of Multiparticulates: Comparison of Aqueous and Organic Coating Techniques

PURPOSE: The purpose of this study was to use polymer blends for the coating of pellets and to study the effects of the type of coating technique (aqueous vs. organic) on drug release. METHODS: Propranolol HCl-loaded pellets were coated with blends of a water-insoluble and an enteric polymer (ethyl cellulose and Eudragit L). Drug release from the pellets as well as the mechanical properties, water uptake, and dry weight loss behavior of thin polymeric films were determined in 0.1 M HCI and phosphate buffer, pH 7.4. RESULTS: Drug release strongly depended on the type of coating technique. Interestingly, not only the slope, but also the shape of the release curves was affected, indicating changes in the underlying drug release mechanisms. The observed effects could be explained by the higher mobility of the macromolecules in organic solutions compared to aqueous dispersions, resulting in higher degrees of polymer-polymer interpenetration and, thus, tougher and less permeable film coatings. The physicochemical properties of the latter were of major importance for the control of drug release, which was governed by diffusion through the intact polymeric films and/or water-filled cracks. CONCLUSIONS: The type of coating technique strongly affects the film microstructure and, thus, the release mechanism and rate from pellets coated with polymer blends.     

Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.     

Influence of processing parameters and formulation factors on the drug release from tablets powder-coated with Eudragit L 100-55.

The aim of this study was to develop a dry powder coating process for chlorpheniramine maleate (CPM) tablets using Eudragit L 100-55 as the delayed release polymer. Powder coating, a water and organic solvent-free process, was investigated as a method to prevent the migration of an ionizable, highly water soluble model drug into the polymeric film during the coating process. Eudragit L 100-55 was pre-plasticized with triethyl citrate (TEC) using hot-melt extrusion at levels of 20%, 30%, and 40%, based on the polymer weight. The extrudate was subsequently cut into pellets and cryogenically ground into a fine powder. Talc was incorporated into the coating powder as an anti-tack agent. PEG 3350 was used as a primer for the powder coating of tablets with pre-plasticized Eudragit L 100-55. The addition of polyethylene glycol 3350 (PEG 3350) to the pre-plasticized Eudragit L 100-55 was necessary to enhance the adhesion of the coating powder to the tablet cores. PEG 3350 also improved film formation and coalescence of the polymeric particles due to its plasticization effects on the acrylic polymer. For comparison, theophylline tablets were also coated with pre-plasticized Eudragit L 100-55. Theophylline was selected as a less water soluble model drug. The powder coating process was performed in a modified laboratory scale spheronizer. The drug release rate was dependent both on TEC content and the coating level. The stability of the powder-coated CPM tablets was confirmed at 25 degrees C/60% RH over a storage time of 12 weeks.     

混合水分散体肠溶迟释薄膜性能研究

目的 采用肠溶型水分散体Eudragit?L30D-55和控释型水分散体Kollicoat?SR30D混合制备一种全新的对周围环境pH值具有响应的,同时具有迟释性能的聚合物薄膜。方法 采用铸膜法制备L30D-55∶SR30D混合水分散体游离膜,采用差示扫描量热法(DSC)测定薄膜玻璃化转变温度(glass transition temperature,Tg),万能材料试验机测试薄膜拉伸性能,杯法考察薄膜透湿性能。考察聚合物比例、附加剂种类和用量对薄膜性能的影响,并以制备泮托拉唑钠(PAZ-Na)肠溶迟释微丸考察包衣膜特性。结果 随着SR30D的增加,薄膜的Tg逐渐降低,强度和刚性变弱,韧性变强,透湿性能先不变后增加。随着增塑剂增加,薄膜刚性减弱,渗透性能增强。不溶性成分的加入可不同程度降低薄膜的渗透性。制备的肠溶迟释微丸在0.1 mol·L^-1盐酸中2 h药物损失量<5%,在pH 6.8缓冲液中可延迟10~20 min开始释放,并至90 min释放完全。结论 L30D-55∶SR30D混合水分散体制备的游离膜和包衣膜具有良好的理化性能,可用于肠溶调释制剂的研究和开发。     

Polymer leaching from film coating: effects on the coating transport properties

The release mechanism of metoprolol succinate pellets coated with a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC), is mechanistically explained. The kinetics of drug release and HPC leaching were followed for drug doses. The coating was initially not permeable to the drug, and release started only after a critical amount of the HPC had been leached out. Drug release occurred mainly through pores created in the coating by the HPC dissolution. Single-pellet release experiments were also performed. The coating thickness and size of each pellet were measured. In order to quantitatively characterize the transport properties of the coating of the individual pellets, and to determine the effective diffusion coefficient (D(e)) of the drug in the coating, a mechanistic model was used to fit the single-pellet release data. It was found that D(e) increased with time due to an increase in the amount of HPC leached. It was also found that D(e) was dependent on the coating thickness, and increased more slowly with a thicker coating. This agreed well with the finding that the HPC leaching rate decreased with increasing film thickness.     

Influence of hydroxyethylcellulose on the drug release properties of theophylline pellets coated with Eudragit RS 30 D.

The objective of this study was to investigate the influence of a hydrophilic polymer, hydroxyethylcellulose (HEC), on the release properties of theophylline from pellets coated with Eudragit RS 30 D, and the physicochemical properties of Eudragit RS 30 D cast films. The release rate of theophylline from Eudragit RS 30 D coated pellets decreased during storage at 25 degrees C/60% RH due to the further coalescence of colloidal acrylic particles. In addition, water-vapor permeability and tensile strength of Eudragit RS 30 D cast film decreased after 1-month storage at 25 degrees C/60% RH. The presence of 10% hydroxyethylcellulose in the coating formulation was shown to stabilize the drug release rate from coated pellets, the water-vapor permeability and the tensile strength of free films. Atomic force microscopy and scanning electronic microscopy were used to demonstrate that the HEC was immiscible with Eudragit RS 30 D in the cast films. The stabilization effect of HEC was investigated and determined to be due to the formation of an incompatible phase between the latex particles which impaired further coalescence of the colloidal acrylic particles.     

Influence of fumed silicon dioxide on the stabilization of Eudragit RS/RL 30 D film-coated theophylline pellets

The objective of this study was to investigate the influence of various grades of fumed silicon dioxide on the drug release rate and physical aging of theophylline pellets coated with Eudragit RS 30 D and RL 30 D. Free films were assessed for both physicomechanical properties and water vapor permeability with respect to time and storage conditions. The release rate of theophylline was influenced by the physical properties of the silicon dioxide employed. As the particle size of the silica dioxide decreased, there was an increase in dispersion viscosity, as well as a decrease in the theophylline release rate from the coated pellets. Films prepared from formulas containing Aeroperl 300 had twice the water vapor transmission rate of films prepared from formulas containing Aerosil 200 VV and Cab-O-Sil M-5P and showed consistent moisture permeability values during storage for up to 1 month at 25 degrees C/0% relative humidity (RH). Scanning electron microscopy (SEM) imaging of pellets coated with a formulation containing Aerosil 200 VV or Cab-O-Sil M-5P demonstrated film structures that were homogenous, while those coated with a formulation containing Aeroperl 300 produced heterogeneous films with large particles of the excipient present within the polymeric matrix of the film. Stability in the drug release rate exhibited by pellets coated with a formulation containing Eudragit RS 30 D, 15% triethyl citrate (TEC), and 30% Aeroperl 300 was attributed to the stabilization of the moisture vapor transmission rate of the acrylic films. Increasing the concentration of Aeroperl 300 in the coating formulation increased the theophylline release rate from coated pellets.     

Application of sucrose fatty acid esters in transdermal therapeutic systems.

Transdermal therapeutic systems (TTSs) were studied applying different sucrose fatty acid esters (SEs) as drug delivery agents. Matrix and membrane controlled TTSs were prepared and compared. Membrane was made from a methacrylic polymer (Eudragit NE) of pH independent permeability which can achieve diffusion controlled drug liberation. Model drug was a water soluble beta-blocker, metoprolol, which has short biological half-life, so applying it in a TTS, the duration of its action could be prolonged. Sucrose fatty acid esters of different fatty acid chain lengths and consequently different hydrophilic-lipophilic balance (HLB) values were studied considering their effect on the metoprolol release from TTSs. Different mathematical models were applied for the evaluation of the release process. The results of the in vitro studies indicated that SEs of shorter fatty acid chain length and higher HLB value increased the amount of released drug about 10 times. SEs could be promising agents in transdermal therapeutic systems to control the drug release and cutaneous absorption.     

Relationship of film properties to drug release from monolithic films containing adjuvants.

The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP-K15 and PVP-K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug-polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present.     

双氯芬酸钠肠溶微丸型片剂的研制

本文制备了双氯芬酸钠肠溶微丸型片剂。以丙烯酸树脂EudragitNE30D和EudragitL30D-55不同比例的混合物作为衣膜材料，对不同粒径大小的双氯芬酸钠速释丸芯进行不同增重水平的包衣，并与不同压缩特性和用量比例的缓冲微丸混合，压片。所得的双氯芬酸钠肠溶微丸型片剂在人工胃液中2 h内累积释放百分数<10%，在人工肠液中1 h内累积释放百分数为(83±2.42)%。结果表明EudragitNE30D与EudragitL30D-55以一定比例混合制备得到适合压片的肠溶微丸，硬脂酸制备的缓冲微丸可用于微丸型片剂的制备。     

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

Mechanical Properties of Dry and Wet Cellulosic and Acrylic Films Prepared from Aqueous Colloidal Polymer Dispersions Used in the Coating of Solid Dosage Forms

The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or water-insoluble), drying or curing conditions, method of film preparation (pseudolatex- vs solvent casting) and ratio of Eudragit RS/RL 30 D in mixed Eudragit RS/RL films. Dry and wet mechanical strengths of the polymeric films depended primarily on the types of the colloidal polymer dispersion and the plasticizer. Films prepared from ethylcellulose dispersions resulted in very weak and brittle films when compared to the acrylic films. Pseudolatex-cast ethylcellulose films showed lower puncture strength and elongation values when compared to those of the solvent-cast films. Curing of the pseudolatex-cast ethylcellulose films had minimal effects on their mechanical properties. Eudragit L 30D, an enteric polymer dispersion, resulted in brittle films in the dry state, but in very flexible films in the wet state because of the plasticization effect of water. Wet Eudragit RS 30 D polymer films plasticized with water-insoluble plasticizers were significantly more flexible than the corresponding wet films plasticized with water-soluble plasticizers. The water-soluble plasticizers leached from the films during exposure to the aqueous medium, while the water-insoluble plasticizers were almost completely retained within the wet films. The low permeability of a water-soluble drug, chlorpheniramine maleate, and the weak mechanical properties of Aquacoat films could suggest osmotic driven/rupturing effects as the release mechanisms from Aquacoat-coated dosage forms.     

Evaluation of acrylic-based modified-release film coatings

Although insoluble pharmaceutical additives have been generally incorporated into film-coating formulations to impart a particular color to a solid dosage form or to reduce tackiness during the coating process, the inclusion of insoluble excipients in Eudragit E 30 D formulations, instead of the commonly used hydrophilic polymers, generated predictable modified-release reservoir systems. Dissolution studies of Eudragit E 30 D-coated pellets indicated that the release profiles depended not only on the physicochemical properties of the drug, particularly solubility, but also on the coating levels and the ratio of the additive to Eudragit resin in the dry film. Moreover, the integrity of the coating material and hence the release rates were found to be independent of the pH of the dissolution medium. Storing the coated pellets below the softening temperature of the Eudragit film for an extended period of time did not lead to a significant change in the release profiles. The predominant mechanism of drug release appears to be diffusion through water-filled pores in the film coat. The pellets were overcoated with a water-soluble hydrophilic polymer to prevent aggregation and enhance flowability. The overcoat did not affect the rate or extent of drug release.     

Study of crystallization of endogenous surfactant in Eudragit NE30D-Free films and its influence on drug-release properties of controlled-release diphenhydramine HCI pellets coated with Eudragit NE30D

This study investigates the crystallization of the endogenous surfactant nonoxynol 100 in Eudragit NE30D-free films during storage and the influences of nonoxynol 100 on the dissolution of diphenhydramine hydrochloric acid (HCL) pellets coated with Eudragit NE30D before and after aging at ambient conditions. Polarizing light microscopy showed that when Eudragit NE30D-free films were stored at ambient conditions, off-white, flower-shaped crystals formed and increased in the polymer film as storage time increased. Also, x-ray diffraction showed polymer crystals in the aged free film. Thermogravimetric analysis showed no evidence of combined volatile molecules with the polymer molecules, and Fourier transformed infrared spectroscopy (FTIR) data suggested the same chemical composition of the polymer before and after phase separation. Further, from normal light microscopy, the appearance of the melting droplets in the polymer film indicated that the polymer molecules did not form the crystals. After the extraction of nonoxynol 100 by water, the free film formed by the water-extracted Eudragit NE30D was found free of the crystals after aging at the same conditions. The combination of the thermogravimetric analysis, FTIR, and microscopy showed that the origin of the crystals in dry Eudragit NE30D-free films came from nonoxynol 100, and not from the polymer molecules themselves. Monitoring by differential scanning calorimeter, it was found that the rates of crystallization of nonoxynol 100 were faster when the films were stored at 30°C and 40°C than when stored at ambient conditions and 45°C. When stored at −5°C, the crystallization rate was nearly zero. As the temperature got closer to melting temperature, the crystallization rate was very low because the system was in a thermodynamically disfavored state. The rate gradually increased and finally passed through a maximum as the crystallization temperature decreased. As the temperature kept decreasing, the crystallization rate became small again and eventually stopped because the system turned into a kinetically disfavored state. Because the phase transition of nonoxynol 100 in Eudragit NE30D occurred at ambient conditions, its influence on the dissolution of diphenhydramine HCL pellets coated with Eudragit NE30D was studied. Three different levels of nonoxynol 100 were used in Eudragit NE30D dispersions to make 3 different batches of Eudragit NE30D film-coated, controlled-release diphenhydramine HCL pellets. The results showed the dissolution rate increased as the level of nonoxynol 100 increased in the coating formula. Compared to the commonly used water-soluble additive human peripheral mononuclear cell, nonoxynol 100 was more effective in enhancing the dissolution of diphenhydramine HCL from pellets coated with Eudragit NE30D. Further study showed that the phase separation of the surfactant during aging tends to stabilize or slightly increase dissolution rates at higher surfactant levels.Key words: Eudragit NE30D, Endogenous Surfactant, Free Film, Diphenhydramine HCL Pellets     

Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit L 100-55

The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder-coated with pre-plasticized Eudragit L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit E PO or Eudragit RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel K4M were incorporated in both Eudragit E PO and Eudragit RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel K4M in the film coating was correlated with their ability to function as pore forming agent.     

Effect of pectinolytic enzymes on the theophylline release from pellets coated with water insoluble polymers containing pectin HM or calcium pectinate

Theophylline pellets were coated with cellulosic (Aquacoat ECD 30, Surelease clear) or acrylic (Eudragit NE30D, RS30D) polymer aqueous dispersions, containing 10% (related to the insoluble polymer content) of pectin HM or calcium pectinate, using a Uni-Glatt fluidized-bed coating apparatus. When commercial pectinolytic enzymes were added to the dissolution media (0.05 M acetate - phosphate buffer, pH 6.0), the release of theophylline from the coated pellets was generally slower than that observed in the media without enzymes. The enzymatic slowing down of the drug release, depending on the type of the aqueous polymer dispersion used, is more important with mixed Eudragit NE/calcium pectinate coated pellets. The results obtained have been examined with regard to the validity of the approach based on the combination of pectins and the insoluble polymer aqueous dispersions intended for specific-delivery of drugs to the colon. The mechanism of the hydrophilic drug release from pellets coated with insoluble polymer aqueous dispersions containing an aqueous gel-forming polymer has been also discussed.     

Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets

Weakly basic drugs and their salts exhibit a decrease in aqueous solubility at higher pH, which can result in pH-dependent or even incomplete release of these drugs from extended release formulations. The objective of this study was to evaluate strategies to set-off the very strong pH-dependent solubility (solubility: 80 mg/ml at pH 2 and 0.02 mg/ml at pH 7.5, factor 4000) of a mesylate salt of weakly basic model drug (pK_a 6.5), in order to obtain pH-independent extended drug release. Three approaches for pH-independent release were investigated: (1) organic acid addition in the core, (2) enteric polymer addition to the extended release coating and (3) an enteric polymer subcoating below the extended release coating. The layering of aspartic acid onto drug cores as well as the coating of drug cores with an ethylcellulose/Eudragit L (enteric polymer) blend were not effective to avoid the formation of the free base at pH 7.5 and thus failed to significantly improve the completeness of the release compared to standard ethylcellulose/hydroxypropyl cellulose (EC/HPC)-coated drug pellets. Interestingly, the incorporation of an enteric polymer layer underneath the EC/HPC coating decreased the free base formation at pH 7.5 and thus resulted in a more complete release of up to 90% of the drug loading over 18 h. The release enhancing effect was attributed to an extended acidification through the enteric polymer layer. Flexible release patterns with approximately pH-independent characteristics were successfully achieved.     

Influence of selected surfactants on the tackiness of acrylic polymer films

Anti-tacking agents are always necessary in polymeric film coating formulations in order to prevent substrate agglomeration. The objective of this study was to investigate the abilities of certain nonionic surfactants in a group of sorbitan ester in reducing the tackiness of the films obtained from aqueous acrylic polymer dispersions (Eudragit), compared with those of talc and glyceryl monostearate (GMS). The results from the peel tests demonstrated that GMS, Span 60 and Span 40 could significantly reduce the tackiness of both Eudragit NE 30D and Eudragit RS 30D films. The mechanisms in reducing the film tackiness were investigated by analyzing the film compositions, using attenuated total internal reflectance infrared spectroscopy (ATR-IR) and optical microscopy. The storage modulus of the films was also examined. The results indicated that GMS, Span 60, and Span 40 could reduce the film tackiness by decreasing the polymer contents at the film surfaces, resulting in a notable reduction in the contact area of the polymers between the surfaces. The use of only 5% (w/w) of either GMS, Span 60 or Span 40 in the coating formulations is enough to prevent pellet agglomeration without adverse effects on film flexibility. The pellets coated with Eudragit RS 30D/RL 30D (9:1, w/w) did not exhibit any difference in the drug release profiles when either 100% (w/w) talc or 5% (w/w) GMS was used, whereas the formulations containing Span 60 or Span 40 gave a slightly faster release rate.     

Correlation between the permeability of metoprolol tartrate through plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films and drug release from reservoir pellets.

The present study investigates if drug diffusion through plasticized isolated ethylcellulose (EC)/hydroxypropyl methylcellulose (HPMC) films prepared by solvent casting can be used as a tool to develop spray-coated dosage forms. In particular, the importance of the level and type of plasticizers was investigated. The permeability of the model drug metoprolol tartrate through plasticized isolated films could be adjusted by selecting the type and amount of plasticizer in the films due to the different hydrophilicity of the plasticizers. The release of metoprolol tartrate from coated pellets is consistent with the drug diffusion through the films made up of the same polymer blends. This indicated that it is useful to test isolated films for early predictions and for formulation optimization.