Capsules For Delivery Research Articles

大腸内圧崩壊型大腸デリバリーカプセルｉｎｔｅｓｔｉｎａｌ ｌｕｍｉｎａｌ ｐｒｅｓｓｕｒｅ‐ｃｏｎｔｒｏｌｌｅｄ ｃｏｌｏｎ ｄｅｌｉｖｅｒｙ ｃａｐｓｕｌｅ（ＰＣＤＣ）のコーティング機による量産法の確立とその大腸送達性評価

A new method for preparing large amounts of intestinal luminal pressure-controlled colon delivery capsule (PCDC) which employs a pharmaceutical coating machine, Hicoater-mini®, has been developed. As a model drug, fluorescein (FL) powder was suspended with suppository base, polyethylene glycol (PEG) 1000, at 50°C, and was hardened in the capsular shape. The capsular shaped suppositories were coated with 5w/v % ethanolic EC (7G grade) solution by a coating machine. By increasing the coating time from 55min to 75min, the mean coating thickness of PCDCs increased. Several kinds of #0 PCDCs having the mean EC coating membrane thickness of 141±7 μm (type 1), 166±4 μm (type 2), 188±4 μm (type 3), 211±4 μm (type 4) as well as #2 PCDCs having thickness of 102±3 μm (type 5) and 110±5 μm (type 6) were administrated to beagle dogs. The mean first appearance times (Tis) of FL into the systemic circulation from #0 PCDCs were 2.3±0.5 for type 1, 3.3±0.5 for type 2, 4.8±1.0 for type 3 and 7.8±1.7hr for type 4 preparations while the mean Tis of #2 PCDCs were 3.2±0.4 for type 5 and 3.8±0.4 hr for type 6, respectively. Therefore, it was suggested that types 2, 3 and 5 PCDCs were delivered to the colon.

Technology to Obtain Sustained Release Characteristics of Drugs after Delivered to the Colon

To determine the necessary technology by which sustained drug release is obtained after drug is delivered to the colon, two kinds of microcapsules were prepared and were filled in a pressure-controlled colon delivery capsule (PCDC). As a model drug 5-aminosalicylic acid (5-ASA) was used, because the target site of 5-ASA is the entire large intestine. 5-ASA was microencapsulated using a water-insoluble polymer, ethylcellulose (EC) or with pH-sensitive polymers, Eudragit™ L-100 or S-100 and encased in PCDC. The particle size of these microcapsules was around 800 μm and the loading efficiencies of 5-ASA were approximately 90%. In vitro dissolution tests were performed with the prepared microcapsules. The release rate of 5-ASA from the microcapsules was significantly prolonged as compared to 5-ASA powder, although there were no significant differences in the release rates between these microcapsules. By incorporating the 5-ASA microcapsules into PCDC, sustained release PCDCs for colon delivery were prepared and in vivo evaluation was performed using beagle dogs. As a fast release colon delivery system, PCDCs were prepared with 5-ASA powder suspended in suppository base. After oral administration of the test preparations to beagle dogs, plasma 5-ASA concentrations were measured and sustained release characteristics of 5-ASA from the test preparations were evaluated from the plasma 5-ASA concentration-time profiles. The first appearance time of 5-ASA into the systemic circulation after oral administration were 3 h for all the colon delivery preparations and it was thought that these test preparations were delivered to the colon. Both EC microcapsules and Eudragit S-100/RS-100 microcapsules in PCDC showed longer the mean residence time MRT, 8.2 ± 0.6 h and 8.7 ± 0.9 h, than Eudragit L-100/RS-100 microcapsules in PCDC where the MRT was 6.6 ± 0.2 h. Since PCDCs containing 5-ASA powder exhibited a MRT of 7.0 ± 1.0 h, these two types of preparations have suggested sustained release characteristics.

生体磁気計測装置による磁気化大腸デリバリーカプセルのヒトにおける大腸送達性の評価 γ‐シンチグラフィーに代わる非侵襲的手法の試み

生体磁気計測装置による磁気化大腸デリバリーカプセルのヒトにおける大腸送達性の評価 γ‐シンチグラフィーに代わる非侵襲的手法の試み

量産化大腸デリバリーカプセルのヒトにおける大腸到達性の評価

量産化大腸デリバリーカプセルのヒトにおける大腸到達性の評価

Evaluation of the feasibility and use of a prototype remote drug delivery capsule (RDDC) for non-invasive regional drug absorption studies in the GI tract of man and beagle dog.

Evaluate a prototype Remote Drug Delivery Capsule (RDDC) for use in beagle dogs and human volunteers for non-invasive drug absorption studies in different regions of the gastrointestinal tract. The device was dual radiolabeled and GI transit of the RDDC was monitored by gamma scintigraphy. Beagles were used initially to demonstrate the functional utility of the device where a solution of ranitidine hydrochloride (150 mg) was non-invasively delivered to the stomach, proximal small intestine and distal small intestine. A subsequent first time in human study enrolled twelve healthy male volunteers where the intended site of release was the stomach, early small bowel, distal small bowel or colon. Preliminary studies conducted in beagles indicated that the RDDC operated successfully and the onset of ranitidine serum levels were dependent on the time of capsule activation and site of drug release. Results from the human study showed that all twelve subjects swallowed the device with no discomfort. Mean gastric emptying of the RDDC was 1.50 +/- 1.28 h (range = 0.25 to 4.25 h), and total small intestine transit was 4.79 +/- 1.82 h (range = 2.00 to 8.25 h). The capsule was retrieved from the feces at 30.25 +/- 15.21 h (range = 14.12 to 74.25 h) and there were no reported adverse events. The prototype RDDC operated successfully in nine of the twelve human volunteers and the cause for the three failures was attributed to mechanical failure while the electronics assembly performed favorably. This prototype remote control capsule was shown to be well tolerated and functional to use in human volunteers as well as beagles. The application of the device coupled with gamma scintigraphy has the potential to be a valuable and rapid method to non-invasively evaluate regional drug absorption in the gastrointestinal tract under conditions that are both pharmaceutically and physiologically meaningful.

Characterization of Norfloxacine Release from Tablet Coated with a New pH-Sensitive Polymer, P-4135F

A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the therapy of patients with Vero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive polymers, Eudragit S100 and L100. To compare the dissolution site of P-4135F coated tablets with other enteric polymer coatings, mini-tablets containing sodium fluorescein (FL) as a model drug were prepared by coating them with the three polymers. After oral administration of FL mini-tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7 ± 0.2h for Eudragit L100, 1.8 ± 0.4 h for S100 and 2.0 ± 0.3 h for P-4135F. Direct inspection of the dissolution process of the FL mini-tablets after oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for P-4135F, at the middle part of the ileum for Eudragit SI00 and at the proximal part of the ileum for Eudragit L100. NFLX tablets with different membrane thicknesses of P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33 ± 0.33 h for 56.8 ± 0.5 μm membranes, 3.75 ± 0.25 h for 64.6 ± 0.7 μm membranes, 4.00 ± 1.00 h for 70.5 ± 0.5 μm membranes and 3.00 ± 1.00 h for 74.9 ± 0.4 μm membranes. By comparing the Ti, 4.33 ± 0.33 h, obtained after oral administration of NFLX in a pressure-controlled colon delivery capsule, and the colon arrival time, 3.5 ± 0.3 h, determined by a sulfasalazine test in beagle dogs, P-4135F coated NFLX tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new polymer will be useful for the delivery of NFLX to the lower part of the small intestine.

Asymmetric membrane capsules for osmotic drug delivery II. In vitro and in vivo drug release performance

In a previous paper, we described asymmetric membrane capsules and a phase inversion process for manufacturing them. In this paper, we describe the in vitro and in vivo drug release characteristics from these capsules. The capsule formulations were developed with model drugs to understand the variables that influenced drug release. Studies were also conducted to understand the drug release mechanism and it was shown that osmotic drug delivery was possible with asymmetric membrane capsules.

Asymmetric membrane capsules for osmotic drug delivery: I. Development of a manufacturing process

This paper describes a novel non-disintegrating polymeric capsule and a manual and a semi-automatic process developed for its manufacture. The capsule wall was made by a phase inversion process in which the membrane structure was precipitated on stainless steel mold pins by dipping the mold pins into a coating solution containing a polymer–solvent–nonsolvent system followed by dipping into a quench solution. The resulting asymmetric membrane wall was composed of a thin dense region supported on a thicker porous region. The asymmetric membrane capsules can be filled with a blend of the active agent and excipients for use in osmotically modulated controlled drug delivery applications.

In vivo drug release behavior in dogs from a new colon-targeted delivery system

The colon-targeted delivery capsule (CTDC), a new capsule-type dosage form for colonic delivery of drugs, was investigated for the in vivo drug release behavior in dogs. A CTDC formulation with prednisolone as a model drug and theophylline as a marker substance for gastric emptying was prepared for this study. The enteric-coated capsule (ECC) formulation with a similar composition was also prepared as the reference. Both formulations were administered to four beagle dogs, and the drug release behavior thereof was compared. Under fasted condition, ECC released prednisolone and theophylline at the same time within 1 h after the gastric emptying. On the other hand the CTDC released prednisolone at 3.2 h after the gastric emptying. Such release behavior of CTDC was approximately consistent with the results obtained from the in vitro dissolution study, suggesting that the pH-sensing and timed-release functions imparted to the CTDC can work in the gastrointestinal tract of dogs as programmed. Under non-fasted condition, however, the gastric emptying of CTDC was found to be considerably delayed, up to about 14 h, and in this case the in vivo dissolution lag time of prednisolone at the small intestine was shortened to about 1.5 h.

New preparation method of intestinal pressure-controlled colon delivery capsules by coating machine and evaluation in beagle dogs

A new method for preparing large amounts of pressure-controlled colon delivery capsules (PCDCs) which employs a pharmaceutical coating machine, Hicoater-mini, has been developed. In contrast to our original method for preparing PCDCs where the inner surfaces of gelatin capsule were coated with the water-insoluble polymer ethylcellulose (EC), PCDC were directly prepared by coating the capsular shaped suppositories with EC. As a model drug, fluorescein (FL) was used in this study. FL powder was suspended with the suppository base, polyethylene glycol (PEG) 1000, at 50°C, and was hardened in the capsular shape the sizes of which were #0 and #2. The capsular shaped suppositories were coated with 5% w/v ethanolic EC (7G grade) solution by a coating machine. By increasing the coating time from 55 to 75 min, the mean coating thickness of #0 PCDCs increased from 141±7 to 211±4 μm. In the case of #2 PDDCs, the mean coating thickness increased from 102±3 to 110±5 μm by increasing the coating time from 35 min to 40 min. Several kinds of #0 PCDCs having the mean EC coating membrane thickness of 141±7 μm (type 1), 166±4 μm (type 2), 188±4 μm (type 3), 211±4 μm (type 4) as well as #2 PCDCs having thickness of 102±3 μm (type 5) and 110±5 μm (type 6) were used for in vivo evaluation using beagle dogs. After oral administration of the test preparations containing 30 mg of FL, blood samples were obtained from the jugular vein and plasma FL levels were measured. The first appearance time, T i, of FL in the plasma was used as a parameter for the estimation of the release time of FL from PCDCs in the gastrointestinal tract. The mean T i of #0 PCDCs were 2.3±0.5 for type 1, 3.3±0.5 for type 2, 4.8±1.0 for type 3 and 7.8±1.7 h for type 4 preparations while the mean T i of #2 PCDCs were 3.2±0.4 for type 5 and 3.8±0.4 h for type 6, respectively. There were good correlations between EC coatings.

The bacterial inhibitory ability and in vivo drug release pattern of a new drug delivery system: ciprofloxacine/tricalcium phosphate delivery capsule.

The bacterial inhibitory ability of a new drug delivery system (DDS): Ciprofloxacine/tricalcium phosphate delivery capsule (CTDC), its in vivo drug release pattern, and the influence of ultrasonic irradiation on its drug release were investigated. It was found that CTDC had a strong and sustained inhibitory ability to some common pathogens of bone and joint infections, such as staphylococcus aureus, escherichia coli and pseudomonas aeruginosa. In vivo drug-release study in animals demonstrated a high concentration of ciprofloxacine in the bone tissue surrounding CTDC which was placed in the greater trochanter of the rabbit and continued to release ciprofloxacine for at least 5 weeks and the blood level of ciprofloxacine was low. In vivo study also showed ultrasonic irradiation could increase the amount of ciprofloxacine released from CTDC, which may be an economical, effecient and safe new method to achieve the control of drug release from DDS.

Scintigraphic Evaluation of a New Capsule-Type Colon Specific Drug Delivery System in Healthy Volunteers

□ Colonic drug delivery is intended for local or systemic therapies. The lack of predictive in vitro or animal model leads to considerable time delays in colonic product development. The objective of this scintigraphic study was to provide “proof of concept” for a novel capsule-type colonic delivery system (Colon-Targeted Delivery Capsule) in healthy volunteers. The human data validates the design concept behind the release mechanism, in that capsule disintegration, and hence drug release, did not start until 5h after gastric emptying, irrespective of whether the product was administered to fasted or fed subjects. However, the potential for prolonged gastric residence for large enteric coated products intended for intestinal targeting was also observed; overall, the study provides a focus for subsequent product development and highlights the role of scintigraphy in dynamically visualizing the drug delivery process.

Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers

The delivery ability of a pressure-controlled colon delivery capsule (PCDC) containing caffeine as a test drug was evaluated after oral administration to healthy male human volunteers. The driving force causing PCDC disintegration in the intestinal tract is the physiological luminal pressure which results from peristalsis. Three kinds of PCDCs having different thickness of a water-insoluble polymer membrane were prepared by coating the inner surface of the gelatin capsules with ethylcellulose (EC). The mean thicknesses were 40±1 (S.E.) for type 1, 44±1 for type 2 and 50±1 μm for type 3 PCDC, respectively. Caffeine was dissolved with a suppository base (PEGs 400 and 1000) and the capsules were filled. Doses were 15, 45 or 75 mg. After blank saliva samples were obtained, test preparations were orally administered to the volunteers and saliva samples were collected for 1 min intervals hourly from 1 to 10 h in the fasted state study, and from 1 to 20 h and at 25 h in the fed state study. Caffeine concentrations in the saliva samples were analyzed by HPLC. The maximum salivary caffeine excretion rate increased as the oral caffeine dose increased. The maximum salivary caffeine excretion rate increased predominantly compared to the pre-dose level in 75 mg dose study. Therefore, all following studies were performed with this dose. The first appearance time of caffeine into the saliva, T i, was used as a parameter to estimate the disintegration time of test preparations in the gastrointestinal tract. The mean T i of types 1, 2, and 3 PCDCs were 3.0±0.4, 4.0±0.4 and 4.5±0.3 h, respectively. After oral administration of 75 mg caffeine in plain gelatin capsule as a reference preparation, caffeine appeared in the saliva within 0.5 h. The mean hardness of the PCDCs were 1.05±0.10 (type 1), 1.55±0.06 (type 2) and 2.08±0.15 newton (type 3), respectively. There were good correlations between three parameters: EC coating membrane thickness, hardness and T i (determination coefficient r 2=0.935 between T i and thickness, r 2=0.998 between thickness and hardness, r 2=0.958 between hardness and T i). The effect of food intake on the delivery ability was examined with type 3 PCDCs. Food intake prolonged the mean T i from 4.5±0.3 to 7.8±1.3 h. This increase is thought to be ascribed to prolonged gastric emptying time. Comparison with reported colon arrival times indicates that the type 3 PCDC functions in colon delivery of caffeine and is thought to be applicable to other drugs.

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean C maxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 μg ml −1, respectively. The mean T maxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 μg·h ml −1, respectively. For FT, C maxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 μg ml −1, and T maxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 μg·h ml −1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean C maxs of liquid preparations and solid preparations were 0.37 and 0.22 μg ml −1, respectively. The mean T maxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 μg·h ml −1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.

Chitosan Capsules for Colon-Specific Drug Delivery: Improvement of Insulin Absorption from the Rat Colon

The objective of this study was to estimate colon-specific insulin delivery with chitosan capsules. In vitro drug release experiments from chitosan capsules containing 5(6)-carboxyfluorescein (CF) were carried out by the Japan Pharmacopoeia (J. P.) rotating basket method with some slight modifications. The intestinal absorption of insulin was evaluated by measuring the plasma insulin levels and its hypoglycemic effects after oral administration of the chitosan capsules containing insulin and additives. Little release of CF from the capsules was observed in liquid 1, an artificial gastric juice (pH1), or in liquid 2, an artificial intestinal juice (pH7). However, the release of CF was markedly increased in the presence of rat cecal contents. A marked absorption of insulin and a corresponding decrease in plasma glucose levels was observed following the oral administration of these capsules that contain 20iu of insulin and sodium glycocholate (PA%=3.49%), as compared with the capsules containing only lactose or only 20IU of insulin (PA%=1.62%). The hypoglycemic effect started from 8h after the administration of chitosan capsules when the capsules entered the colon, as evaluated by the transit time experiments with chitosan capsules. These findings suggest that chitosan capsules may be useful carriers for the colon-specific delivery of peptides including insulin.

A new drug delivery system--ciprofloxacine/tricalcium phosphate delivery capsule (CTDC) and its in vitro drug release pattern.

A new drug delivery system (DDS), ciprofloxacine/tricalcium phosphate delivery capsule (CTDC) was developed by loading a broad-spectrum antibiotic ciprofloxacine into the central cylindrical cavity of tricalcium phosphate capsule. The new system showed good biocompatibility and could degrade gradually in our preliminary studies. In vitro study showed that CTDC could maintain high-level and long-term release of ciprofloxacine and that ultrasonic irradiation within the range of physical therapy could increase the drug release amount from CTDC ( P < 0.02), and might become a new technique to achieve the control of drug release from DDS.

Application of a Colon Delivery Capsule to 5-Aminosalicylic Acid and Evaluation of the Pharmacokinetic Profile after Oral Administration to Beagle Dogs

Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the dose of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.

水不溶性高分子Ｅｔｈｙｌｃｅｌｌｕｌｏｓｅを用いた大腸デリバリーカプセルのヒトにおける消化管内到達性の評価

水不溶性高分子Ｅｔｈｙｌｃｅｌｌｕｌｏｓｅを用いた大腸デリバリーカプセルのヒトにおける消化管内到達性の評価

ペプチド・蛋白質性薬物の大腸デリバリーシステム

The advances in biotechnology and medicinal chemistry in 1980s made it possible to produce large amount of useful peptide/protein drugs. However, their clinical use is limited to parenteral route. Among them, we selected recombinant human granulocyte-colony stimulating factor (rhG-CSF) as a representative peptide/protein drug. For the sake of the QOL of patients, non-parenteral, especially oral, preparation is needed now. For the development of oral peptide/protein preparations, colon delivery system has attracted the interests of many scientists. The most important reason is the lower hydrolytic enzyme activities in the colon than in the small intestine. We have developed two colon delivery capsules (CDC). One is intestinal inner pressure-controlled CDC (PCDC) and the other is release time-controlled CDC. As PCDC does not receive the effect of food on the delivery efficiency of drugs to the colon, PCDC was used for the preparation of oral rhG-CSF. At first, the colon delivery ability of PCDC was ascertained by administering 5-aminosalicylic acid (5-ASA), a drug for inflammatory bowel disease, in PCDC. After oral administration of 5-ASA in PCDC to beagle dogs, plasma 5-ASA levels vs. time curves were analyzed. The first appearance time of 5-ASA into the systemic circulation was approximately 4hr which corresponds to the colon arrival time in the beagle dogs. Based on these results, rhG-CSF was formulated into the PCDC and was orally administered to beagle dogs, 25 μg/kg. Blood samples were collected consecutively for 96 hr and blood total leukocyte counts (BTLC) were measured. At 8 hr after administration, BTLC increased to 1.3 times higher than the pre-dose level and thereafter declined gradually to the normal level at 96 hr. These results support the usefulness of PCDC for designing the oral delivery system of peptide/protein drugs.

エチルセルロース製大腸デリバリーカプセルの大腸疾患治療薬への適用

We have developed a pressure-controlled colon delivery capsule (PCC) made of ethylcellulose and reported its application to a protein drug, recombinant human granulocyte colony-stimulating factor (rhG-CSF) in last year. In this report, PCC was applied to the drugs for colon diseases, and the relationship between the drug release characteristics from colon delivery systems and bioavailability (BA) was investigated using Eudragit S coated tablet as a reference solid preparation. As model drugs, 5-aminosalicylic acid (5-ASA) and tegafur (FT) were selected. With each drug, PCC and Eudragit S coated tablet were prepared, and these test preparations were administered to fasted male beagle dogs and drug concentration in the systemic circulation was measured by HPLC methods. In addition, the in vitro dissolution tests were performed according to JP XIII method. Mean AUC values of 5-ASA, 25 mg/kg, were 22. 57 for Eudragit S coated tablet and 48.09 μg·h/ml for PCC, respectively. On the other hand, mean AUG values of FT, 1 mg/kg, were 9.73 for Eudragit S coated tablet and 15.55 μg·h/ml for PCC. Mean AUC values of PCC were significantly higher than those of Eudragit S coated tablets, with two drugs. On the other hand, the in vitro dissolution test showed that the release rate of drug from tablet delayed as compared to that from PCC. As less water is present in the colon than in the small intestine, it was speculated that in the case of Eudragit S coated tablet, the solid materials inside the colon such as stools decreased both the amount and the time of drug molecules being contact to the gut wall, and drug molecules were not well dissolved by the gastrointestinal fluid, because solid preparation was used. Both the release rate from PCC and the dissolution rate of drugs were improved, because PCC can contain drug molecules as liquid state. In conclusion, PCC is thought to be safe and useful colon delivery system for the oral delivery of protein drugs and drugs for colon diseases.