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 (T(lag)), 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 T(lag) and increase of k. T(lag) 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 T(lag) and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T(lag), 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.     

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 3h 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.     

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.     

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.     

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 (T_lag), 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 T_lag and increase of k. T_lag 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 T_lag and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T_lag, 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.     

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 degrees 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.     

Modified release from hydroxypropyl methylcellulose compression-coated tablets

The goal of this study was to obtain flexible extended drug release profiles (e.g., sigmoidal, pulsatile, increasing/decreasing release rates with time) with hydroxypropyl methylcellulose (HPMC) compression-coated tablets. Drugs of varying solubility (carbamazepine, acetaminophen, propranolol HCl and chlorpheniramine maleate) were incorporated into the tablet core in order to evaluate the flexibility/limitations of the compression-coated system. The HPMC-compression-coating resulted in release profiles with a distinct lag time followed by different release phases primarily determined by the drug solubility. Carbamazepine, a water-insoluble drug, was released in a pulsatile fashion after a lag time only after erosion of the HPMC compression-coat, while the more soluble drugs were released in a sigmoidal fashion by diffusion through the gel prior to erosion. With carbamazepine, increasing the molecular weight of HPMC significantly increased the lag time because of the erosion-based release mechanism, while, in contrast, molecular weight did not affect the release of the more soluble drugs. The lag-time and the release rate could also be well controlled by varying the HPMC amount in and the thickness of the compression-coating. A pulsatile release could also be achieved for water-soluble drugs by introducing an enteric polymer coating between the drug core and the HPMC compression-coating. This novel concept of introducing an enteric subcoating eliminated drug diffusion through the gelled HPMC layer prior to its erosion. Incorporating drug in the compression-coating in addition to the tablet core in varying ratios resulted in release profiles with increasing, decreasing or constant release rates. In conclusion, a versatile single-unit delivery system for a wide range of drugs with great flexibility in release profiles was presented.     

Development of time-, pH-, and enzyme-controlled colonic drug delivery using spray-dried chitosan acetate and hydroxypropyl methylcellulose.

A colonic drug delivery with a new concept based on a combination of time-, pH-, and enzyme-controlled system was developed. Spray-dried chitosan acetate (CSA) prepared from low molecular weight chitosan was characterized. A combination of CSA and hydroxypropyl methylcellulose (HPMC) was used as new compression-coats for 5-aminosalicylic acid (5-ASA) tablets. Factors affecting in-vitro drug release, i.e. % weight ratio of coating polymers, enzyme activity, pH of media, and excipients in core tablets, were evaluated. The tablets compression-coated with HPMC:CSA at 60:40 and 50:50% weight ratio providing lag times about 5-6h were able to pass through the stomach (stage I, 0.1N HCl) and small intestine (stage II, pH 6.8, Tris-HCl). The delayed release was time- and pH-controlled owing to the swelling with gradual dissolving of CSA and HPMC in 0.1N HCl and the less solubility of CSA at higher pH. After reaching the colon (stage III, pH 5.0, acetate buffer), the dissolution of CSA at low pH triggered the drug release over 90% within 14h. Furthermore, the degradation of CSA by beta-glucosidase in the colonic fluid enhanced the drug release while adding the disintegrant or the osmotic agent in the core tablets would affect the drug release.     

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.     

Programmable Drug Delivery from an Erodible Association Polymer System

An erodible association polymer system based on blends of cellulose acetate phthalate (CAP) and Pluronic F127, a block copolymer of poly(ethylene oxide) and poly(propylene oxide), has been investigated for its applicability to rate-programmed drug delivery. The compatibility and thermal properties were characterized by DSC and FTIR. Results from the thermal analysis indicate that the blends are compatible above 50% CAP, as revealed by a single composition-dependent glass transition temperature (T _g). The existence of molecular association through intermolecular hydrogen bonding between the carboxylic acid and the ether oxygen groups is supported by the observation of an upward shift in the IR carbonyl stretching frequency at increasing Pluronic F127 concentrations. Using theophylline as a model drug, the in vitro polymer erosion and drug release characteristics of the present polymer system were evaluated at different buffer pH's on a rotating-disk apparatus. The results show that the rates of both polymer erosion and drug release increase with the Pluronic F127 concentration in the blend. Further, at pH 4, the polymer erosion is minimal and the theophylline release appears to be governed mainly by diffusion through the polymer matrix. In contrast, at pH 7.4, the theophylline release is controlled primarily by the polymer surface erosion. To demonstrate the unique approach to programmed drug release based on the concept of non-uniform initial drug distribution, pulsatile patterns of drug release have been achieved successfully from the present surface-erodible polymer system using a multilaminate sample design with alternating drug-loaded layers. The results suggest that the pulsing frequency and peak rate of such pulsatile drug delivery are pH dependent; however, they can be modulated by varying the thickness, drug loading, and erosion rate of the constituent layers in the multilaminate.     

Hydrophobic weak acid polymers as controlled release carriers

Poly(carboxyalkyl methacrylates) were studied as a cationic-drug delivery system, at pH 6.8 and 8.0. Different polymer/drug complexes were used to prepare compressed tablets. By kinetics experiments, we have found that drug release is dependent on both the hydrophobicity of the whole complex and the pH of the environment. Furthermore, a mechanism of dissociation/erosion clearly describes the drug release from a complex formed by a polymer soluble at target pH; otherwise, a mechanism of dissolution/diffusion is depicted. Additionally, we have observed that hydrophilic fillers increase the drug release rate. Since our results using different polymer/drug complexes exhibit pH-sensitive drug release, we propose that the poly(carboxyalkyl methacrylates) have potential as a colon-specific drug-delivery system.     

Hydrophobic weak acid polymers as controlled release carriers

Poly(carboxyalkyl methacrylates) were studied as a cationic-drug delivery system, at pH 6.8 and 8.0. Different polymer/drug complexes were used to prepare compressed tablets. By kinetics experiments, we have found that drug release is dependent on both the hydrophobicity of the whole complex and the pH of the environment. Furthermore, a mechanism of dissociation/erosion clearly describes the drug release from a complex formed by a polymer soluble at target pH; otherwise, a mechanism of dissolution/diffusion is depicted. Additionally, we have observed that hydrophilic fillers increase the drug release rate. Since our results using different polymer/drug complexes exhibit pH-sensitive drug release, we propose that the poly(carboxyalkyl methacrylates) have potential as a colon-specific drug-delivery system.     

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points. Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1 (core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.     

卡维地洛脉冲释放片的制备及体外释药特征

目的：制备卡维地洛脉冲释放片并考察其体外释药特征。方法：采用压制包衣法制备卡维地洛定时脉冲释放片,紫外分光光度法测定卡维地洛药物含量,以体外释放度为主要评价指标,考察崩解剂、包衣材料等对脉冲片释药性能的影响,并对处方进行优化。结果：处方中片芯含药量为10%,以63%的CMS-Na为崩解剂,27%的MCC为填充剂压制片芯;以35%的HPMC、62.5%的卡拉胶和1%的PEG 6000为衣膜材料,2.5%的滑石粉为润滑剂,粉末直接压片包衣。以pH4.0醋酸缓冲液为释放介质,包衣脉冲片时滞8 h后,累积释放度达80%以上。结论：卡维地洛压制包衣片能实现定时脉冲释药效果。     

Development and in vitro evaluation of a mucoadhesive vaginal delivery system for nystatin

The purpose of the present study was to design and evaluate a novel vaginal delivery system for nystatin based on mucoadhesive polymers. L-Cysteine and cysteamine, respectively, were covalently attached to poly(acrylic acid), and the two different thiolated polymers were evaluated in vitro regarding their swelling behavior, mucoadhesive properties and release behavior. Tablets comprising these thiolated polymers and nystatin demonstrated a high stability in vaginal fluid simulant pH 4.2 and an increase in weight by swelling whereas control tablets comprising unmodified poly(acrylic acid) disintegrated and dissolved. The mucoadhesion time of tablets on freshly excised bovine vaginal mucosa on a rotating cylinder and the total work of adhesion of gels and tablets increased significantly due to the formation of disulfide bonds between the thiolated polymer and cysteine rich subdomaines of the mucus layer. The drug nystatin was released more slowly out of thiomer tablets and gels than out of PAA control tablets and gels. Therefore these thiolated polymers are promising delivery systems for nystatin providing a prolonged residence time and a sustained drug release in vitro under physiological relevant conditions.     

Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate

The influence of in situ plasticization of chlorpheniramine maleate (CPM) on Eudragit RS PO from hot-melt extruded matrix tablets, and from compressed granules prepared by thermal processing was investigated. CPM was studied as both a model drug substance and as a solid-state plasticizer for the acrylic polymer. Triethyl citrate (TEC) was incorporated into the polymer blend as a liquid plasticizer for the polymer. The influence of TEC and CPM concentration on the dissolution properties of CPM tablets was investigated. The glass transition temperature (T(g)) of the samples was determined by modulated differential scanning calorimetry (MDSC). The morphologies of the granules formed by hot-melt extrusion and hot-melt granulation processes were investigated by scanning electron microscopy. The addition of 12% TEC to the polymer reduced the T(g) by 32.5 degrees C, while the reduction in the T(g) for the same level of CPM was 16.4 degrees C. The effect of TEC levels on drug release was dependent on the tablet preparation method. At high TEC levels, the release rate of CPM decreased in tablets prepared by direct compression and tablets made from compressed granules that had been prepared by high shear hot-melt granulation. However, the CPM release rate increased from hot-melt extruded tablets with increasing blends of plasticizer in the extruded tablets. An increase in the CPM content in the tablets resulted in an increase in the drug release rate. During high shear hot-melt granulation, the model drug adhered to the polymer to form a porous discontinuous structure. Following hot-melt extrusion, the drug was distributed at a molecular level in the continuous polymeric structure. The influence of both CPM and TEC levels on the drug release rate from these polymeric drug delivery systems was shown to be a function of whether the granules or tablets were formed by either hot-melt granulation or hot-melt extrusion, as well as the plasticization effects of both TEC and CPM on the acrylic polymer.     

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.     

Structure formation and characterization of injectable drug loaded biodegradable devices: In situ implants versus in situ microparticles

The objective of the study was to investigate key formulation variables affecting the release of bupivacaine hydrochloride, a local anesthetic, from different in situ forming biodegradable drug delivery devices. The formulations included ISM systems [in situ microparticles, a poly(lactide)-solvent phase dispersed into an external oil phase] and poly(lactide) solutions (in situ implant systems). The solubility of the biodegradable polymer poly(d,l-lactide) (PLA) in various organic solvents was determined using the Hansen multicomponent solubility parameter concept. The solvent release from ISM and polymer solutions into phosphate buffer which influences the polymer precipitation rate was investigated as a function of the type of solvent, polymer concentration and polymer:oil phase ratio by using a HPLC assay. Scanning electron microscopy (SEM) was performed in order to relate the drug release to the surface properties of the precipitated implants or microparticles. Suitable solvents for the preparation of the in situ forming drug delivery systems, such as N-methyl-2-pyrrolidone (NMP), dimethylsulfoxide (DMSO) and 2-pyrrolidone were found using the Hansen multicomponent solubility parameter concept. The injection of the polymer solutions (in situ implants) into the aqueous medium led to a rapid solvent/non-solvent exchange. The resulting in situ implants were porous, thus explaining the rapid initial drug release. Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles as shown by SEM measurements. Due to the presence of an external oil phase the solvent release into the buffer medium from ISM was significantly slower compared to the polymer solutions. The solvent release of the ISM systems into the phosphate buffer decreased with increasing polymer concentration and decreasing polymer:oil phase ratio. The type of solvent used also affected the solvent release. A slower solvent release into the aqueous medium resulted in less porous microparticles, thus explaining the reduced initial drug release from ISM systems compared to the polymer solutions.     

New insights on poly(vinyl acetate)-based coated floating tablets: Characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength

The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.     

An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin

Abstract

The use of pectin for colon-specific drug delivery has been extensively investigated; however, when used alone, pectin is often compromised due to its high solubility. This study explored the feasibility of using an in situ compression-coated crosslinking system, composed of pectin and calcium chloride, for colon-specific drug delivery. A pectin/calcium chloride (P/Ca) coating was compressed onto a core tablet. The colon specificity of the compression-coated tablet was verified by dissolution, pharmacokinetics and scintigraphy with ^99mTc labeling. The in situ pectin and calcium chloride gel slowed the release of indomethacin. The lag time varied between 3?h and 7?h depending on the amount of calcium chloride and the coating weight. Pectinase triggered the release of indomethacin from the compression-coated tablet, which was then accelerated by the calcium chloride in the coating layer. The compression-coated tablet had a prolonged t_max and apparent t_1/2, as well as a decreased C_max and AUC_0–t, compared with the core tablet counterpart. Evaluation with γ-scintigraphy verified colon-specific delivery of the compression-coated tablet. In conclusion, the P/Ca in situ crosslinking system worked well for colon-specific drug delivery.