Compression-coated Tablets Research Articles

Improved drug delivery to the lower intestinal tract with tablets compression-coated with enteric/nonenteric polymer powder blends

The objective of this study was to develop pH-erosion-controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression-coatings of powder blends of the enteric polymer Eudragit® L100-55 and the extended release polymer ethylcellulose. Tablet cores containing model drugs of varying solubilities (acetaminophen, carbamazepine and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit® L100-55:ethylcellulose 10cP FP at different compression forces and tablet core:compression-coat ratios. The compression-coated tablets were characterized by drug release, media uptake, erosion behaviour and wettability. All drugs were released in a pulsatile fashion in higher pH-media after a lag time, which was controlled by the erosion properties of the Eudragit L:ethylcellulose compression-coating. The addition of ethylcellulose avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Importantly, ethylcellulose also reduced the pH-dependency of the erosion process between pH 5.5 and 7.4. The lag time could also be increased by increasing the compression force and decreasing the core:compression-coat ratio. In conclusion, tablets compression-coated with blends of Eudragit L and ethylcellulose resulted in excellent release properties for potential targeting to the lower intestinal tract with no release in lower pH-media and rapid release after a controllable lag time in higher pH-media.

Preparation of delayed release tablet dosage forms by compression coating: Effect of coating material on theophylline release

In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox® exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox®/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

Innovation of novel sustained release compression-coated tablets for lornoxicam: formulation and in vitro investigations

Objective: The objective of this study was to modify the release characteristics of lornoxicam, a highly potent nonsteroidal anti-inflammatory drug, by preparing compression-coated tablets (CCTs) that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain prolonged analgesic effect as well as meets the reported sustained release specifications. Methods: Each of the prepared CCTs was composed of a sustained release tablet core and an immediate release coat layer. Amorphous, well-characterized, freeze-dried solid dispersion of lornoxicam with polyvinylpyrrolidone K-30 was employed in the coat layer to attain an initial rapid dissolution of lornoxicam in the stomach, assuring rapid onset of analgesic effect. Compritol® ATO 888, a lipophilic matrix-forming material, was included in the core tablets to sustain lornoxicam release. Lactose was also incorporated into these core tablets to ensure complete release of lornoxicam in a time period comparable to the gastrointestinal residence time. Results: All the prepared CCTs showed acceptable physical properties that complied with compendial requirements. On the basis of in vitro drug release studies, performed in simulated gastric and intestinal fluids in sequence to mimic the gastrointestinal transit, CCTs belonging to formulations F3 CCTs and F4 CCTs were able to show the desired release profile. Conclusion: This study demonstrated the possibility of modulating lornoxicam release using CCTs to meet the reported sustained release specifications.

Innovation of novel sustained release compression-coated tablets for lornoxicam: formulation and in vitro investigations

The objective of this study was to modify the release characteristics of lornoxicam, a highly potent nonsteroidal anti-inflammatory drug, by preparing compression-coated tablets (CCTs) that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain prolonged analgesic effect as well as meets the reported sustained release specifications. Each of the prepared CCTs was composed of a sustained release tablet core and an immediate release coat layer. Amorphous, well-characterized, freeze-dried solid dispersion of lornoxicam with polyvinylpyrrolidone K-30 was employed in the coat layer to attain an initial rapid dissolution of lornoxicam in the stomach, assuring rapid onset of analgesic effect. Compritol ATO 888, a lipophilic matrix-forming material, was included in the core tablets to sustain lornoxicam release. Lactose was also incorporated into these core tablets to ensure complete release of lornoxicam in a time period comparable to the gastrointestinal residence time. All the prepared CCTs showed acceptable physical properties that complied with compendial requirements. On the basis of in vitro drug release studies, performed in simulated gastric and intestinal fluids in sequence to mimic the gastrointestinal transit, CCTs belonging to formulations F3 CCTs and F4 CCTs were able to show the desired release profile. This study demonstrated the possibility of modulating lornoxicam release using CCTs to meet the reported sustained release specifications.

Optimization of Budesonide Compression-Coated Tablets for Colonic Delivery

The purpose of this study was to formulate budesonide (BUD) compression-coated tablets for colonic specific delivery. Pectin and guar gum were used as enzyme-dependent polymers. For comparison purposes, both pH- and time-dependent polymers were also tried. In vitro release studies were carried out at different pH (1.2, 6.8, and 7.4). Therapeutic efficacy of the prepared tablets compared to commercially available capsules and enema were evaluated in trinitrobenzenesulfonic acid-induced rabbit colitis model. In pH-dependent polymers, Eudragit (EUD) S100/EUD L100 (1:1) released 45.58% in the target area (colon). For time-dependent polymers, decreasing cellulose acetate butyrate (CAB) ratio increased the release in both pH 6.8 and 7.4 till it reached 40.58% and 93.65%, respectively, for 25% CAB. In enzyme-dependent polymers, increasing pectin ratio to 75% retarded the release (4.59% in pH 6.8 and 54.45% in pH 7.4) which was significantly enhanced to 99.31% using pectinolytic enzyme. Formula F14 coated with 75% pectin significantly reduced the inflammatory cells in the connective tissue core of the colon of the treated group and significantly decreased myeloperoxidase activity (3.90 U/g tissue weight). This study proved that BUD compression-coated with 75% pectin may be beneficial in the treatment of inflammatory bowel disease.

Characterization of 5-Fluorouracil Release from Hydroxypropylmethylcellulose Compression-Coated Tablets

Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (Tlag), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of Tlag and increase of k. Tlag and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in Tlag and decrease in k. There was good fitting of a linear model for each of the four variables W, D, Tlag, and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.

Development of colon-targeted albendazole-β-cyclodextrin-complex drug delivery systems

Albendazole, a drug for the treatment of gastrointestinal nematode infection, is variably and erratically absorbed from the gastrointestinal tract after oral administration. The present study was aimed at developing matrix tablets of albendazole using guar gum as carrier for colon targeting in order to provide an effective and safe therapy for helminthiasis. To improve its bioavailability, the formation of inclusion complexes of albendazole with β-cyclodextrins was investigated. Matrix tablets of albendazole–β-cyclodextrin complex were prepared by the wet granulation method using guar gum as matrix carrier in various proportions: 20% (SAC-20), 30% (SAC-30), and 40% (SAC-40). A high-performance liquid chromatography–ultraviolet method was developed to quantitate albendazole using mebendazole as internal standard at 254 nm. The granules were compressed using 12-mm round, flat, and plain punches. Tablets were evaluated for various physical characteristics such as thickness, hardness, and drug content uniformity. The matrix tablets were subjected to in vitro drug release studies in 0.1 N HCl (2 h), pH 7.4 Sorensen's phosphate buffer (3 h) and simulated colonic fluids. The SAC-30 released 67.7±1.9% of albendazole in the presence of rat caecal contents, whereas in the control study the formulation released only 29.7±0.2% of albendazole. A significant difference (P<0.001) was observed at 24 h in the amount of albendazole released from SAC-30 when compared to the dissolution study without rat caecal contents. The study shows that the release of albendazole in the physiological environment of colon is due to the microbial degradation of guar gum compression-coated tablets in the presence of rat caecal contents. Stability studies were carried out at 40°C/75% relative humidity for 6 months to assess their long-term (2 years) stability. No change either in their physical appearance or in drug content was observed. Drug Dev. Res. 65:76–83, 2005. © 2005 Wiley-Liss, Inc.

In vivo evaluation of time and site of disintegration of polysaccharide tablet prepared for colon-specific drug delivery

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to evaluate a formulation with a considerably reduced coat weight and gum concentration for colonic drug delivery in vivo using gamma scintigraphy. In vitro studies have found this formulation to be useful for delivery of 5-fluorouracil to the colon. Rapidly disintegrating core tablets containing 99mTc-DTPA were prepared and compression coating with 150 mg of granules containing a mixture of xanthan (XG), guar gum (GG) and starch. The ratios of the two gums XG:GG in the coat was kept 10:20. In vitro dissolution studies on XG:GG::10:20 tablets containing 99mTc-DTPA were carried out in simulated upper GIT conditions and also in presence of colonic contents. Cumulative percent release of technetium in the upper GIT conditions and transit time amounted to 4%. The total amount of technetium released in the 24 h of the dissolution study was 53 ± 3.23%. Upon introduction of cecal content into the dissolution medium (4%), the release of technetium from the compression-coated tablet increased to 78.34 ± 5.34%. Gamma scintigraphy studies carried out in six healthy human volunteers showed that the tablet remained intact during its transit through the upper GIT. The anatomical site of disintegration was found to be the ascending colon/hepatic flexure and the disintegration of the tablet started between 4 and 6 h post-dose in all the volunteers with a further spread of tracer into the ascending, transverse, descending and sigmoidal colon.

A novel compression-coated doughnut-shaped tablet design for zero-order sustained release.

A novel coated doughnut-shaped tablet is evaluated as to its ability to be manufactured in a reproducible manner, and as to whether it releases model drugs at a zero-order rate. The doughnut-shaped tablets were compressed using specially designed punches, which make automated production feasible. In the preliminary part of the experiment, HPMC K15M mixed with gelatin was found to be the most suitable coating tablet material with respect to its disintegration and adherence properties. The adherence of the coating tablet to ibuprofen cores was not optimal, so different concentrations of gelatin, to act as a plasticiser and enhance adherence, were further investigated. Friability results of the coated doughnut-shaped tablet indicate that coating tablets containing 20% and 30% gelatin had a percentage weight losses of less than 1% after 100 revolutions in a Roche friabilator. For all the concentrations of gelatin, the granule blends had angle of repose values in the range of 22.01-17.8 degrees. The compressibility factor, as measured from the slopes of the natural logarithm of compressional force versus crushing strength, were 121.91 +/- 2.36, 132.64 +/- 3.60, and 88.54 +/- 11.52 for the coating tablet granules containing 10%, 20%, and 30% gelatin in HPMC K15M, respectively. The composition of the coating tablet did not affect the rate of release of both caffeine and ibuprofen from the coated doughnut-shaped tablets. The coatings also adhered to the core tablets for the entire duration of the release of the drugs.

Poly( N-isopropylacrylamide) copolymers for constant temperature controlled drug delivery

In the course of the development of a new drug delivery concept, four thermosensitive copolymers of poly( N-isopropylacrylamide) (PNIPAAm), with phase transition temperature slightly higher than 37 °C, were synthesised and used as time-controlled drug delivery agents. For this purpose, compression-coated tablets coated with the thermosensitive copolymers and containing Na 2SO 4 were prepared and in vitro dissolution tests were performed at constant physiological temperature, the lag time before drug release being controlled by the amount of Na 2SO 4 incorporated into the form. Due to the salting out effect, the lag time was increased by up to 80–90% for PNIPAAm-co-NVA and PNIPAAm-co-MVA coated tablets.

A new index, the core erosion ratio, of compression-coated timed-release tablets predicts the bioavailability of acetaminophen

Although compression-coated tablets are a commonly used timed-release drug delivery technology, their utility is often limited by poor bioavailability. To try to improve the bioavailability of these tablets, the effect of their core composition of compression-coated tablet on in vivo pharmacokinetics was investigated. First, the extent of mass reduction of cores in different compression-coated tablet core formulations was used to establish a new index, the core erosion ratio. The data show that adding excipients with high water solubility to the core results in a greater core erosion ratio. Next, to elucidate the effect of core erosion ratio on in vivo acetaminophen (AAP) release, three compression-coated tablet formulations with similar in vitro AAP release profiles but different core erosion ratios were administered to four fasted dogs. The time for first appearance (TFA) of AAP in plasma did not differ significantly among formulations, indicating that the in vivo lag time was the same for all formulations. In separate experiments, necroscopy revealed that 3 h after oral administration, the tablets were located in the ileum and colon and that all three formulations had identical GI transit times. However, the area under the AAP plasma concentration–time curve was greater in dogs given formulations with larger core erosion ratios. These results suggest that a formulation with a large core erosion ratio can significantly increase in vivo drug release from compression-coated tablets, leading to increased drug absorption from the lower GI tract.

Studies on the Development of Colon Targeted Oral Drug Delivery Systems for Ornidazole in the Treatment of Amoebiasis

The aim of the present study is to develop colon-targeted drug delivery sytems for ornidazole using guar gum as a carrier. The core formulation containing ornidazole was directly compressed. Compression-coated tablets of ornidazole containing various proportions of guar gum in the coat were prepared. All the formulations were evaluated for hardness and drug content uniformity and were subjected to in vitro drug release studies. The amount of ornidazole released from tablets at different time intervals was estimated by the HPLC method. The compression-coated formulations released less than 8% of ornidazole in the physiological environment of stomach and small intestine. The compression-coated tablets with 85%, 75%, and 65% of guar gum coat released about 21%, 38%, and 73% of ornidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression-coated ornidazole tablets with either 65% (OLV-65) or 75% (OLV-75) of guar gum coat are most likely to provide targeting of ornidazole for local action in the colon owing to its minimal release of the drug in the first 5 hr. The ornidazole compression-coated tablets showed no change in physical appearance, drug content, or in dissolution pattern after storage at 40°C/75% relative humidity for 6 months.

In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil

Intravenous administration of 5-fluorouracil for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The broad objective of the present study was to develop novel tablet formulations for site-specific delivery of 5-fluorouracil to the colon without the drug being released in the stomach or small intestine using guar gum as a carrier. Fast-disintegrating 5-fluorouracil core tablets were compression coated with 60% (FHV-60), 70% (FHV-70) and 80% (FHV-80) of guar gum, and were subjected to in vitro drug release studies. The amount of 5-fluorouracil released from the compression-coated tablets in the dissolution medium at different time intervals was estimated by a HPLC method. Guar gum compression-coated tablets released only 2.5–4% of the 5-fluorouracil in simulated GI fluids. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) the compression-coated FHV-60, FHV-70 and FHV-80 tablets released another 70, 55 and 41% of the 5-fluorouracil respectively. The results of the study show that compression-coated tablets containing 80% (FHV-80) of guar gum are most likely to provide targeting of 5-fluorouracil for local action in the colon, since they released only 2.38% of the drug in the physiological environment of the stomach and small intestine. The FHV-80 formulation showed no change either in physical appearance, drug content or dissolution pattern after storage at 40 °C/RH 75% for 6 months. The differential scanning calorimetric study showed that 5-fluorouracil did not interact with the formulation excipients used in the study.

Evaluation of a new controlled-drug delivery concept based on the use of thermoresponsive polymers

The purpose of this work is to develop a new delivery concept making a thermosensitive polymer based on poly( N-isopropylacrylamide) (PNIPAAm) useful as a time-controlled drug release device, without any temperature changes of the dissolution medium. It was previously found that some salts induce a decrease of the polymer lower critical solution temperature (LCST). Use is here made of that property to show that salt concentration variations can be used as a substitute for temperature changes to make the polymer coating of compression-coated tablets soluble or insoluble, consequently creating a possible new concept of drug delivery control from delivery systems containing thermoresponsive polymers. The obtained results show the influence of the type and amount of salts incorporated into compression-coated tablets on the release lag time of a model drug.

An Investigation of the Influence of the Core Material Properties on the Compression and Properties of Dry-Coated Tablets

The effect of core material properties on the process of compression and physical properties of compression-coated tablets were investigated using microcrystalline cellulose as the coating material (mantle). Three model core materials: borosilicate glass, silicone rubber, and steel, each of different Young's modulus, were selected to give a range of core mechanical properties. Coated tablets were prepared using a single-punch press, with facilities for monitoring the compression cycle and analysis of data using the Heckel (1) equation. This analysis showed a considerable effect of different core materials on the compression process, (i) as an unanchored core, and (ii) due to core material type with differing Young's modulus.

L1.6 Time-controlled drug release from compression-coated tablet formulations : M Halsas Div. of Biopharmaceutics and Pharmacokinetics, Dept. of Pharmacy, POB 56, FIN-00014 Univ. of Helsinki

L1.6 Time-controlled drug release from compression-coated tablet formulations : M Halsas Div. of Biopharmaceutics and Pharmacokinetics, Dept. of Pharmacy, POB 56, FIN-00014 Univ. of Helsinki

Permeability of [ 3H]water across a porous polymer matrix used as rate-limiting shell in compression-coated tablets

Compression coating was investigated for use in preparing controlled release dosage forms having a polymer shell surrounding a soluble core. The purpose of the study was to develop a method of measure flux and permeability of water across the outer shell (coat) of the compression-coated tablet. One half of the shell of the press-coated tablets was mounted on the platform of the receptor port of the Thomas diffusion cell by embedment in white petrolatum. The cumulative amount of tritium labeled water per square centimeter permeating across the barrier was plotted vs time, and flux, lag time, diffusion coefficient and permeability were calculated from the steady-state slope. No difference was found whether the outside or inside of the membrane was exposed to the donor phase. The lag time increased linearily and significantly from 0.3 to 0.79 to 1.1 h with increasing shell thickness from 1.08 to 1.66 to 2.12 mm, respectively. Flux and permeability decrease hyperbolically with increasing shell thickness. Increasing hardness at constant shell amount significantly increases lag time and decreases flux and permeability. Compression-coating seems to be a viable technique for preparation of controlled release drug delivery systems with a wide range for adjustment of permeability.