Influence of an enteric polymer on drug release rates of theophylline from pellets coated with Eudragit RS 30D

The purpose of this research study was to investigate the influence of an enteric polymer on the drug release properties of theophylline pellets coated with Eudragit RS 30D. Theophylline pellets were coated with aqueous colloidal dispersions of Eudragit RS 30D containing various amounts of Eudragit L 100-55. The effect of storage conditions on the release of drug from coated pellets was determined as a function of the pH of the dissolution medium. The results from the dissolution study showed significant changes in the dissolution rate of theophylline from pellets coated with Eudragit RS 30D when cured at 40 degrees C for 4 days. No change in the drug release rate was observed when Eudragit L100-55 was present in the Eudragit RS 30D dispersion. Increasing the ratio of Eudragit L100-55 to Eudragit RS 30D resulted in faster drug release rates from the coated pellets. An increase in the pH of the dissolution medium was found to enhance drug release from the pellets coated with Eudragit RS 30D containing Eudragit L 100-55. Theophylline pellets when coated with Eudragit RS 30D containing the enteric polymer Eudragit L100-55 demonstrated no aging effects when stored at elevated temperatures. The overcoating of the pellets with Eudragit RD 100 did not affect the drug release profiles and prevented the particles from agglomerating during curing and storage.     

Design of pH-independent controlled release matrix tablets for acidic drugs

The rate and extent of drug release from most controlled release systems are influenced by the pH of the dissolution medium for drugs with pH-dependent solubility. This dependency of drug release on pH may lead to additional inter- and intra-subject variability in drug absorption. In the present study, a pH-independent controlled release matrix system for acidic drugs was designed by incorporating release-modifiers in the formulation. Controlled release matrix tablets were prepared by compression of divalproex sodium, Methocel K4M and Eudragit E 100 or Fujicalin as the release-modifier. For formulations without any release-modifier, the extent and rate of drug release at pH 6.8 was much higher than that at pH 1.0. Formulations containing Eudragit E 100 provided drug release that was essentially independent of pH. This was achieved because Eudragit E 100 significantly increased the drug release in acidic medium and slightly decreased the release rate at higher pH. The increased release in the acidic medium can be attributed to the elevation of the micro-environmental pH in the swollen polymer gel layer. Formulations containing Fujicalin were less effective than those containing Eudragit E 100. This was attributed to the relative inability to elevate the pH and shorter residence time of Fujicalin in the matrix relative to Eudragit E 100.     

Relationship between drug dissolution and leaching of plasticizer for pellets coated with an aqueous Eudragit S100:L100 dispersion

In order to investigate the relationship between drug dissolution and leaching of plasticizer, theophylline pellets coated with 30% (w/w) Eudragit S100:L100 (1:1) plasticized with different levels of triethyl citrate (TEC) were prepared. The influence of storage conditions on the dissolution profile of theophylline and leaching of TEC was determined. Theophylline was found to dissolve completely from pellets coated with Eudragit S100:L100 (1:1) plasticized with 50% TEC at pH 6.0 after 2h. The shape of the pellets was maintained during dissolution testing. Cracks due to the leaching of TEC were observed in the scanning electron micrographs (SEMs) following dissolution testing at pH 6.0. Both the dissolution of theophylline and the leaching of TEC decreased during storage due to further coalescence of the acrylic polymers. The dissolution profiles of theophylline showed a biphasic pattern and the lag times were estimated as the time points at which a second, rapid release of theophylline was initiated. Subsequently, the percent of TEC leached at the lag time was calculated. While the lag time was increased by storage time and humidity, the percent of TEC leached at the lag time was unchanged as a function of storage condition and was dependent on the initial TEC levels in the films. In conclusion, the plasticizer content in the film coating influenced the dissolution profile of theophylline from pellets coated with Eudragit S100:L100 (1:1). A large amount of the TEC was leached from the enteric films before drug release was initiated and a TEC level of approximately 30% in the films, based on the polymer weight, was the critical amount of TEC for initiating drug release during dissolution testing at pH 6.0. While enteric films are more soluble and dissolve faster at higher pH values, the kinetics of plasticizer release was one of the important factors controlling the dissolution of drugs at pH 6.0, at which pH the enteric polymers were insoluble.     

Development of novel budesonide pellets based on CODES(TM) technology: In vitro/in vivo evaluation in induced colitis in rats

Background and the purpose of the study

Budesonide is the drug of choice for treatment of active inflammatory bowel disease (IBD). The aim of this study was to develop budesonide pellets based on a novel colon drug delivery system (CODES).

Methods

Pellet cores containing lactulose or mannitol were prepared by extrusion/spheronization and coated with an acid soluble polymer (Eudragit E100), hydroxypropylmethyl cellulose (HPMC) and an enteric coat (Eudragit FS 30D) sequentially. In vitro drug release of coated pellets was studied using USP dissolution apparatus type II in buffers of pH 1.2 (2 hrs), pH of 7.4 (4 hrs) and pH of 6.8 containing 8% rat cecal contents (RCC) (18 hrs). The efficacy of the optimized formulation (containing 50% lactulose coated with Eudragit E (30% w/w) and Eudragit FS 30D (12% w/w)) was evaluated against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Results

The results of the kind of bacteria in vitro dissolution tests indicated absence of drug release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8 containing RCC. It was found that release rate was controlled by the type and amount of polysaccharide and the thickness of the acid soluble layer. The prepared formulation showed promising results in alleviating the conditions of experimental model of colitis.

Conclusion

The results of this study suggest that pellets based on CODES technology could be useful for colonic delivery of budesonide.     

硝苯地平膜控型控释微丸的制备及体外评价

目的研究硝苯地平(NF)膜控型24 h控释微丸的处方与工艺,并考察其体外释放特性。方法采用液相层积、丸芯上药法制备载药速释微丸,以Eudragit RL100、RS100为包衣材料,流化床悬浮包衣法制备膜控型控释微丸,并对影响微丸释放的处方因素进行了考察。通过与市售渗透泵片拜新同的体外释放度的对比研究,探讨硝苯地平膜控型控释微丸的体外释药特征。结果调整Eudragit RL100、RS100的比例、衣层厚度、致孔剂的用量,可以改变药物的释放速率。当Eudragit RL100、RS100的比例为3∶7,包衣增重为6%时,制备的控释微丸体外释药与市售渗透泵片相似(f2=62.8),具有良好的零级释放特性。结论以丸芯上药法,Eudragit RL100、RS100为控释材料制备的NF膜控型控释微丸,具有良好的零级释放特性,结果可为硝苯地平多单元控释制剂的研究开发提供参考。     

磷酸川芎嗪丙烯酸树脂水分散体包衣小丸的体外释放研究

目的：研究磷酸川芎嗪丙烯酸树脂水分散体包衣缓释小丸的体外释药。方法：采用丙烯酸树脂RS30D和丙烯酸树脂RL30D混合液包衣制备磷酸川芎嗪缓释小丸，并考察包衣混合液中两种丙烯酸树脂水分散体比例、包衣增重、溶出介质pH对磷酸川芎嗪包衣制剂体外释药的影响。结果：随着包衣液中丙烯酸树脂RL30D/丙烯酸树脂RS30D比例增大、包衣增重降低、溶出介质pH增大，释药速率加快。结论：包衣液中丙烯酸树脂RL30D/丙烯酸树脂RS30D比例、包衣增重、溶出介质pH均显著影响制剂药物释放。     

Design and evaluation of pH modulated controlled release matrix systems for colon specific delivery of indomethacin

Indomethacin, a potent non steroidal anti-inflammatory drug (NSAID), is indicated for the local treatment of colorectal carcinoma. The aim of the present study was to design and investigate various matrix systems for controlled and site specific delivery of indomethacin to the colon. Various pH sensitive and hydrophobic polymers were investigated for their effect on drug release and site specificity. Effect of proportion of Eudragit L100 and Eudragit S100 in matrix either alone or in combination was evaluated. Effect of hydrophobic non-swellable polymer ethyl cellulose on the release pattern of drug from the Eudragit bases was also investigated. Matrix tablets prepared with Eudragit showed pH dependent release profile with the formulations of Eudragit L100 showing faster rate of drug release than Eudragit S100 in alkaline pH. The release profile from matrix tablets containing Eudragit L100 and Eudragit S100 in combination or with ethyl cellulose correlated well with the relative proportion of the two polymer types in the matrix base. Selected formulations when evaluated in simulated gastric fluid pH without enzymes showed negligible to low drug release (less than 10%) in the first 4-6 h followed with controlled release for 14-16 h. It was concluded that pH sensitive matrix bases in combination with a hydrophobic polymer like ethyl cellulose canbe ideal for site specific delivery of drugs to colon with controlled release profile.     

Preparation and evaluation of Eudragit gels. II: In vitro release of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels.

The in vitro dissolution characteristic of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels was investigated by the rotation disk method. The dissolution pattern of salicylic acid and erosion of Eudragit L polymer from the organogels followed apparent zero-order kinetics, providing strong evidence for a surface erosion mechanism and negligible diffusional release of salicylic acid. On the other hand, the dissolution of salicylic acid from Eudragit S organogels was a linear function of the square root of time. The apparent dissolution rate of salicylic acid from Eudragit S organogels increased with increasing temperature from 32 to 42 degrees C and agitation rate from 50 to 200 rpm. A linear relationship was obtained between the logarithm of apparent dissolution rate constants and the reciprocal of absolute temperatures. The activation energy for release of salicylic acid from Eudragit S organogels was in the range of 2.99 to 5.57 kcal/mol. From various experimental results, it was concluded that the release process of salicylic acid from Eudragit S organogels was diffusion controlled through the organogels matrix.     

Statistical optimization of indomethacin pellets coated with pH-dependent methacrylic polymers for possible colonic drug delivery

The objective of this study was to evaluate the effect of two factors (ratio of Eudragit S100 and Eudragit L100 and the coating level) on indomethacin release from pellets in order to optimize coating formulations for colonic delivery. Coating formulations were designed based on the full factorial design. Two independent variables were the ratio of Eudragit S100:Eudragit L100 (1:4, 1:1 and 1:0) and the level of coating (10%, 15% and 20%, w/w), respectively. The evaluated responses were lag time prior to drug release at pH 6.8 (the time required for drug release up to 2%) and percent of drug release at pH 6.8 in 5h. Polymers were coated onto the pellets containing 20% (w/w) indomethacin, using a fluidized bed coating apparatus. Dissolution test was carried out in media with different pH (1.2, 6.5, 6.8 and 7.2). The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve optimum formulation. Using responses and resulted statistical equations, optimum formulation consisted of Eudragit S100:L100 in 4:1 ratio and the level of coating (20%) was predicted. Practical results showed that the pellets prepared according to above formulation released no indomethacin at pH 1.2 (simulating stomach pH) and pH 6.5 (simulating proximal part of small intestine pH); drug release was slowly at pH 6.8 (simulating lower part of small intestine pH), but it was fast at pH 7.2 (simulating terminal ileum pH). The results of this study revealed that factorial design is a suitable tool for optimization of coating formulations to achieve colon delivery. It was shown that coating formulation consisted of Eudragit S100:Eudragit L100 in 4:1 ratio at 20% coating level has potential for colonic delivery of indomethacin loaded pellets. The optimized formulation produced dissolution profiles that were close to predicted values.     

Physical characterization and dissolution properties of ibuprofen: Eudragit coprecipitates.

Ibuprofen:Eudragit coprecipitates were prepared in 10:3 ratios and their physical properties and related dissolution characteristics were determined. The Eudragit polymers used for the studies were three anionics (Eudragit L100, Eudragit L100-55, and Eudragit S-100), one anionic:cationic mixture used in a 1:1 ratio (Eudragit S100 + E100), and four zwitterionics (Eudragits RL 100, RS 100, RSPM, and RLPM). Physical characterizations were made using qualitative and quantitative X-ray diffractometry, IR spectrophotometry, and differential scanning calorimetry (DSC). Except for Eudragit S100 + E100 coprecipitates, no sizeable interaction at a molecular level was detected between the drug and the polymer. The crystalline structure of the drug was slightly modified in the coprecipitates. Regardless of the lack of interaction, dissolution of ibuprofen was retarded from all the coprecipitates studied (except Eudragit L100), especially in the pH 6.8 to 7.5 media in which the drug is freely soluble. The dissolution rate constants of the coprecipitates, calculated using Higuchi equation, demonstrated that dissolution decreased in the order of anionics greater than zwitterionic greater than anionic + cationic mixtures. The data obtained suggest that the release mechanisms involved are the swelling and slower dissolution of the polymer matrix relative to precipitated ibuprofen. The coprecipitates possess improved flow properties compared with ibuprofen with the exception of Eudragit RLPM and Eudragit RSPM. Eudragit coprecipitates can be useful tools in preparing ibuprofen sustained-release tablets. The coprecipitation technique used is simple and minimizes the use of organic solvents.     

Understanding and Managing the Impact of HPMC Variability on Drug Release from Controlled Release Formulations

The purpose of this study is to identify critical physicochemical properties of hydroxypropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1664–1672, 2014     

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.     

Combination of time-dependent and pH-dependent polymethacrylates as a single coating formulation for colonic delivery of indomethacin pellets

The objective of this study was to evaluate the combination of pH-dependent and time-dependent polymers as a single coating for design of colon delivery system of indomethacin pellets. Eudragit S100 and Eudragit L100 were used as pH-dependent polymers and Eudragit RS was used as a time-dependent polymer. A statistical full factorial design was used in order to optimize formulations. Factors studied in design were percent of Eudragit RS in combination with Eudragit S and L and coating level. Dissolution studies of pellets in the media with different pH (1.2, 6.5, 6.8 and 7.2) showed that drug release in colon could be controlled by addition of Eudragit RS to the pH-dependent polymers. The lag time prior to drug release was highly affected by coating level. With combination of two factors, i.e. the percent of Eudragit RS and coating level, the optimum formulation was found to be the one containing 20% Eudragit RS, 64% Eudragit S and 16% Eudragit L, and a coating level of 10%. This formulation was reproduced and tested in continuous condition of dissolution, and also separately at pH 7.5. The results of in vitro experiments indicate that the proposed combined time-dependent and pH-dependent polymethacrylate polymer coating may provide a colonic delivery system for indomethacin.     

Release of furosemide from multiple-unit and single-unit preparations containing different viscosity grades of sodium alginate

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while high viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero-order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.     

Thermal treating as a tool to produce plastic pellets based on Eudragit RS PO and RL PO aimed for tableting.

A 3(2) full-factorial design was used for preparation of pellets using extrusion-spheronization technique. Independent variables were %ibuprofen (40, 60, 80) and %Eudragit RS PO/RL PO (0, 50, 100). In all formulations 3% w/w PVP K30 and 10% Avicel PH101 were also used. The pellets were cured in oven at 60 degrees C for 24h. The evaluated responses were crushing strength or yield point, elastic modulus and mean dissolution time (MDT) of pellets. The cured pellets were also compressed at 15kN compaction force and then observed under scanning electron microscope. It was shown that the cured pellets containing 40% or 60% drug exhibited a plastic deformation without any fracture under mechanical tests. The curing process resulted in significant decrease in the elastic modulus of the pellets. The SEM of the compressed pellets were also confirmed the plastic behavior of these pellets. The transition of pellet behavior from brittle to plastic upon curing was due to shift of Eudragit structure from glassy to rubbery state which was supported by DSC studies. However pellets with 80% drug showed brittle properties even after curing due to presence of less amount of Eudragit in their structure. Increasing the ratio of Eudragit RS in the pellets decreased the yield point and elastic modulus of cured pellets containing 40% or 60% drug, indicating more plastic behavior of these pellets. This was attributed to lower Tg of Eudragit RS than Eudragit RL. The curing process also retarded drug release from pellets and increased MDT. Increasing the ratio of Eudragit RS in the pellets increased MDT in cured pellets containing 40% or 60% drug but had no effect in pellets with 80% drug. Overall the results of this study revealed that thermal treating is a proper tool to produce plastic ibuprofen pellets based on Eudragit RS PO and Eudragit RL PO.     

Citric acid monohydrate as a release-modifying agent in melt extruded matrix tablets

Incomplete drug release and particle size-dependent dissolution performance can compromise the quality of controlled release matrix systems. The objective of the current study was to investigate the ability of citric acid monohydrate (CA MH) to enhance the release of diltiazem hydrochloride from melt extruded Eudragit((R)) RS PO tablets and to eliminate drug particle size effects. Preformulation studies demonstrated the thermal stability of all components, drug insolubility in the polymer but miscibility with the CA MH. Tablets with either constant polymer levels or constant drug-to-polymer ratios and containing different drug particle size fractions and increasing amounts of CA MH were manufactured by melt extrusion and characterized by dissolution testing, powder X-ray diffraction and scanning electron microscopy. The addition of CA MH to the formulation promoted the thermal processibility and matrix integrity by plasticization of the polymer. The drug release from systems with constant drug-to-polymer ratio was significantly increased when CA MH was added as a result of enhanced pore formation. Particle size effects were eliminated when large amounts of CA MH were used due to the loss of drug crystallinity. Matrix tablets with CA MH furthermore showed a faster and more complete drug release compared to systems with drug only or alternative pore formers (sucrose, NaCl, or PEG 3350). The enhanced drug release was attributed to the amorphous character of the soluble components, improved drug dispersion in the plasticized polymer along with increased polymer permeability. In summary, CA MH promoted the miscibility between the drug and Eudragit((R)) RS PO during hot-melt extrusion, resulting in the extrusion of an amorphous system with improved dissolution characteristics.     

Release of Furosemide from Multiple-Unit and Single-Unit Preparations Containing Different Viscosity Grades of Sodium Alginate

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while hh viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero–order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.     

Inorganic-polymer nanohybrid carrier for delivery of a poorly-soluble drug, ursodeoxycholic acid

Delivery of poorly soluble drugs has been problematic due to its low absorption profile and bioavailability. In this work, ursodeoxycholic acid (UDCA), a poorly-soluble drug, was intercalated into inorganic nanovehicle, layered double hydroxides (LDHs), with a molecular level to enhance its solubility in biological fluid. The UDCA-loaded nanovehicle (i.e., UDCA-LDHs) was also coated with an anionic polymer, Eudragit(?) S100, to increase the dissolution rate of UDCA. According to the powder X-ray diffraction (PXRD) patterns of UDCA-LDHs, the gallery height of LDHs was expanded from 3.6? to 28.3?, indicating that the UDCA molecules were successfully intercalated into the interlayer space of LDHs. Fourier transform infrared (FT-IR) spectra also revealed that the UDCA molecules were well stabilized in the LDHs through electrostatic interaction. The in vitro dissolution test in a simulated biological fluid (pH=6.8) showed that the total dissolved fraction of UDCA for the first 2h was about 60.2% for the Eudragit(?) S100 coated UDCA-LDHs, which was a dramatic increase as compared with 19.0% dissolution from intact UDCA. It is, therefore, concluded that LDHs nanovehicle coated with an anionic polymer is a promising delivery system for improving aqueous solubility of poorly soluble drugs.     

Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process

The objectives of this study were to investigate the particle size distribution, morphology and dissolution properties of spherical pellets produced by hot-melt extrusion and spheronization and to compare the properties of hot-melt extruded pellets with beads manufactured by a traditional wet-mass extrusion and spheronization method. Spherical pellets were produced by hot-melt extrusion without the use of water or other solvents. A powder blend of theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 was hot melt-extruded and the resulting composite rod was cut into cylindrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. The same powder blend was processed using conventional wet-mass techniques. Unlike wet-mass extruded pellets, pellets prepared from hot-melt extrusion displayed both a narrow particle size distribution and controlled drug release in dissolution media less than pH 7.4. Scanning electron microscopy, X-ray diffraction and porosity measurements were employed to explain the differences in drug release rates of theophylline from pellets produced by the two processing techniques. Theophylline release from the hot-melt extruded pellets was described using the Higuchi diffusion model, and drug release rates from wet-granulated and melt-extruded pellets did not change after post-processing thermal treatment.     

Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism

The present study deals with controlled drug delivery from hydrocolloid tablets by polymer particle erosion. The influence of excipients and formulation factors on the dissolution behaviour of the methyl hydroxyethyl cellulose (MHEC)-tablets is investigated. Linear drug release with low susceptibility to hydrodynamic stress is obtained. The use of drugs with higher solubility leads to a slight acceleration of the release due to the contribution of diffusion to the release process. Higher drug loading and consequently lower polymer content expedites dissolution as well as changes in the tablets' geometry resulting in enlarged release surfaces. Furthermore, alterations of the composition of the dissolution medium affect drug release. However, neither viscosity grade nor the particle size of the polymer or compaction pressure has a marked impact on the dissolution. Investigations to clarify the mechanism of polymer particle erosion include erosion studies and the comparison of different batches of MHEC, of products from different manufacturers and of fibrous trial products. There is evidence that the insoluble fibres within the water soluble MHEC are responsible for the occurrence of polymer particle erosion by disturbing swelling and formation of a thick coherent gel layer and thus, causing erosion of the hydrocolloid tablet with synchronous drug release.