pH-Sensitive oral insulin delivery systems using Eudragit microspheres

In this paper, we present in vitro and in vivo release data on pH-sensitive microspheres of Eudragit L100, Eudragit RS100 and their blend systems prepared by double emulsion-solvent evaporation technique for oral delivery of insulin. Of the three systems developed, Eudragit L100 was chosen for preclinical studies. Insulin was encapsulated and in vitro experiments performed on insulin-loaded microspheres in pH 1.2 media did not release insulin during the first 2?h, but maximum insulin was released in pH 7.4 buffer media from 4 to 6?h. The microspheres were characterized by scanning electron microscopy to understand particle size, shape and surface morphology. The size of microspheres ranged between 1 and 40?µm. Circular dichroism spectra indicated the structural integrity of insulin during encapsulation as well as after its release in pH 7.4 buffer media. The in vivo release studies on diabetic-induced rat models exhibited maximum inhibition of up to 86%, suggesting absorption of insulin in the intestine.     

Eudragit Coating of Chitosan-Prednisolone Conjugate Microspheres and In Vitro Evaluation of Coated Microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch‐SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

Eudragit coating of chitosan-prednisolone conjugate microspheres and in vitro evaluation of coated microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch-SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery

The purposes of this study were to develop and evaluate calcium pectinate/alginate microspheres (PAMs) and to exploit their pH-sensitive properties for colon-targeted delivery of encapsulated cisplatin. PAMs were prepared using an electrospraying method. The PAMs, as cores, were then coated with Eudragit S100 using a polyelectrolyte multilayer coating technique in aqueous solution. The morphology of the microspheres was observed under scanning electron microscopy. In vitro drug release studies were performed in simulated gastrointestinal fluid, and the results indicated that approximately 5 % of the cisplatin was released from the Eudragit S100-coated PAMs, and 51 % of the cisplatin was released from the uncoated PAMs at 1 h. The release of cisplatin from the Eudragit S100-coated PAMs was more sustained in simulated gastric fluid than in simulated intestinal fluid due to the increased solubility of the coating polymer in media with pH >7.0. Drug release from the Eudragit S100-coated PAMs was best described by the Higuchi’s square root model. From these results, it was concluded that Eudragit S100-coated PAMs are a potential carrier for delivery of cisplatin to the colon.     

Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm⁻¹. XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07°C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 μm. Storage of the microspheres at 40°C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.     

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins, II. Combination Resin Formulations

Theophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness between the range of 6.8 kg to 15 kg showed minimal influences on the dissolution rate. Recompression and relubrication of the tablet formulation containing both polymers, produced a decrease in release rates of theophylline from the tablet matrix.     

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins,II. Combination Resin Formulations

Abstract

Theophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness between the range of 6.8 kg to 15 kg showed minimal influences on the dissolution rate. Recompression and relubrication of the tablet formulation containing both polymers, produced a decrease in release rates of theophylline from the tablet matrix.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

Abstract

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.     

Effect of Various Polymers on Formulation of Controlled Release (CR) Ibuprofen Tablets by Fluid Bed Technique

The need for controlled release (CR) formulations of ibuprofen tablet, is well recognized. Some such formulations have been marketed but in general only patented.

The purpose of this study was to develop an air suspension method, using a laboratory scale fluidized bed drier to coat the ibuprofen granules. Different polymers including, Eudragits L100, S100, RL100, RS100, L100+S100 (1:1), RL100+RS100 (1:1), ethyl cellulose (EC) and Eudragit RS100+EC (1:1) were utilized. The drug release medium consisted of buffer pH 1.2 for 1st 2h, buffer pH 4.5 for 2nd 2h and buffer pH 7.5 for remaining period of time in all experiments, but the release behaviour of the drug from some formulations was also studied using distilled water. Of the polymers investigated, Eudragit RS100, EC, Eudragit S100 and Eudragit RS100+EC (1:1) exhibited proper release characteristics when used as coating materials. The release patterns were analyzed from the standpoint of diffusion-controlled processes and as first-order kinetics.     

Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro-in vivo evaluation

Gastric emptying is a complex process that is highly variable and makes the in vivo performance of drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug delivery systems for more than 12 hours utilizing floating or hydrodynamically controlled drug delivery systems. The objective of this investigation was to develop a floating, depot-forming drug delivery system for an antidiabetic drug based on microparticulate technology to maintain constant plasma drug concentrations over a prolonged period of time for effective control of blood sugar levels. Formulations were optimized using cellulose acetate as the polymer and evaluated in vitro for physicochemical characteristics and drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in healthy male albino mice. The shape and the surface morphology of the prepared microspheres were characterized by optical microscopy and scanning electron microscopy. In vitro drug release studies were performed and drug release kinetics were calculated using the linear regression method. Effects of stirring rate during preparation and polymer concentration on the size of microspheres and drug release were observed. The prepared microspheres exhibited prolonged drug release (more than 10 hours) and remained buoyant for over 10 hours. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 73% to 98% were obtained. The release rate decreased and the mean particle size increased at higher polymer concentrations. Stirring speed affected the morphology of the microspheres. This investigation revealed that upon administration, the biocompatible depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain orally given drug. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.     

Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system

Objective: Simple Eudragit microparticles loaded with prednisolone and chitosan-succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system.

Materials and methods: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions.

Results: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 μm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 μm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8.

Conclusions: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features.     

Preparation of the Traditional Chinese Medicine Compound Recipe Heart-Protecting Musk pH-Dependent Gradient-Release Pellets

ABSTRACT

In this study a sustained-release formulation of traditional Chinese medicine compound recipe (TCMCR) was developed by selecting heart-protecting musk pills (HPMP) as the model drug. Heart-protecting musk pellets were prepared with the refined medicinal materials contained in the recipe of HPMP. Two kinds of coated pellets were prepared by using pH-dependent methacrylic acid as film-forming material, which could dissolve under different pH values in accordance with the physiological range of human gastrointestinal tract (GIT). The pellets coated with Eudragit L30D-55, which dissolves at pH value over 5.5, were designed to disintegrate and release drug in the duodenum. The pellets coated with Eudragit L100–Eudragit S100 combinations in the ratio of 1:5, which dissolve at pH value 6.8 or above, were designed to disintegrate and release drug in the jejunum to ileum. The pellets coated with HPMC, which dissolves in water at any pH value, were designed to disintegrate and release drug in the stomach. Finally, the heart-protecting musk sustained-release capsules (HPMSRC) with a pH-dependent gradient-release pattern were prepared by encapsulating the above three kinds of coated pellets at a certain ratio in hard gelatin capsule. The results of dissolution of borneol (one of the active compounds of the TCMCR) in vitro demonstrated that the coating load and the pH value of the dissolution medium had little effect on the release rate of borneol from pellets coated with hydroxypropyl methyl cellulose (HPMC), but had a significant effect on the release rate of borneol from pellets coated with Eudragit L30D-55 or Eudragit L100–Eudragit S100 combinations in the ratio of 1:5. The pellets coated with Eudragit L30D-55 at 30% (w/w) coating load or above had little drug release in 0.1 mol/L HCl for 3 hr and started to release drug at pH value over 5.5. The pellets coated with Eudragit L100–Eudragit S100 combinations in the ratio of 1:5 at 36% (w/w) coating load or higher had little drug release in 0.1 mol/L HCl for 3 hr and in phosphate buffer of pH value 6.6 for 2 hr, and started to release drug at pH value 6.8 or above. The release profiles of lipophilic bornoel and hydrophilic total ginsenoside from HPMSRC, consisting of three kinds of pellets respectively coated at a certain ratio with HPMC, Eudragit L30D-55, and Eudragit L100–Eudragit S100 in the ratio of 1:5, showed a characteristic of pH-dependent gradient release under the simulated gastrointestinal pH conditions and no significant difference between them. The results indicated that various components with extremely different physicochemical properties in the pH-dependent gradient-release delivery system of TCMCR could release synchronously while sustained-releasing. This complies with the organic whole concept of compound compatibility of TCMCR.     

Basic drug--enterosoluble polymer coevaporates: development of oral controlled release systems

Precipitation of basic drugs within oral prolonged release systems, at the higher pH values of the intestine, would affect drug release. Coevaporates of a model basic drug verapamil HCl, in single or mixed polymer systems, containing Eudragit L100 (L100) and ethyl cellulose or Eudragit RS100, were prepared from ethanolic solution. XRD and DSC indicated loss of crystallinity of the drug in the coevaporates. The presence of the enterosoluble polymer in the system was found to aid in faster dissolution of the drug at higher pH values. This was affected by the presence and type of retarding polymer present in the system. Compression of the coevaporates resulted in either very slow release of the drug or undesirable changes in the release profile. Pelletization of a coevaporate containing drug and L100 yielded systems, which released the drug uniformly when studied by the buffer change method in simulated gastric (SGF) and intestinal (SIF) fluids. The presence of L100 in intimate contact with the drug was found to be essential for the desirable drug release properties of the system. The drug release occurred predominantly by diffusion in SGF and by a combination of diffusion and polymer dissolution/erosion in SIF. Appropriate choice of release modifiers and formulation variables and development of suitable formulations can yield systems which compensate for the reduced solubility of the drug in the higher pH environments of the intestine.     

Preparation and bioavailability of sustained-release doxofylline pellets in beagle dogs

The objective of this study was to develop doxofylline-loaded sustained-release pellets coated with Eudragit NE30D alone (F1) or blend of Eudragit RL30D/RS30D (F2) and further evaluate their in vitro release and in vivo absorption in beagle dogs. Doxofylline-loaded cores with a drug loading of 70% (w/w) were prepared by layering drug-MCC powder onto seed cores in a centrifugal granulator and then coating them with different kinds of polymethacrylates in a bottom-spray fluidized bed coater. Dissolution behaviour of these formulations was studied in vitro under various pH conditions (from pH 1.2 to pH 7.4) to evaluate the effect of pH on drug release profiles. It was found that F2 produced a better release profile than F1 did and two different release mechanisms were assumed for F1 and F2, respectively. The relative bioavailability of the sustained-release pellets was studied in six beagle dogs after oral administration in a fast state using a commercially available immediate release tablet as a reference. Coated with Eudragit NE30D and a blend of Eudragit RL30D/RS30D (1:12), at 5% and 8% coating level, respectively, the pellets acquired perfect sustained-release properties and good relative bioavailability, with small fluctuation of drug concentration in plasma. But combined use of mixed Eudragit RL30D/RS30D polymers with proper features as coating materials produced a longer T(max), a lower C(max) and a little higher bioavailability compared to F1 (coated with Eudragit NE30D alone). The C(max), T(max) and relative bioavailability of F1 and F2 coated pellets were 15.16 microg/ml, 4.17 h, 97.69% and 11.41 microg/ml, 5 h, 101.59%, respectively. Also a good linear correlation between in vivo absorption and in vitro release was established for F1 and F2, so from the dissolution test, formulations in vivo absorption can be properly predicted.     

Preparation and characterization of insulin nanoparticles employing chitosan and poly(methylmethacrylate/methylmethacrylic acid) copolymer

As most of polypeptides are marginally stable, a mild formulation procedure would be beneficial for the activities of these drugs. The objective of the present study was to develop a novel pH-sensitive nanoparticle system that was suitable for entrapment of hydrophilic insulin but without affecting its conformation. Chitosan was incorporated as a positively charged material, and one of the three poly(methylmethacrylate/methylmethacrylic acid) copolymers, consisting of Eudragit L100-55, L100, and S100, was used as a negatively charged polymer for preparation of three insulin nanoparticles, respectively. Three nanoparticles obtained were spherical. The mean diameters were in the range from 200 nm to 250 nm, and the entrapment efficiencies, from 50% to 70%. The surface analysis indicated that insulin was evenly distributed in the nanoparticles. Polymer ratio of chitosan to Eudragit was the factor which influenced the nanoparticles significantly. Characterization results showed that the electrostatic interactions existed, thus providing a mild formulation procedure which did not affect the chemical integrity and the conformation of insulin. In vitro release studies revealed that all three types of the nanoparticles exhibited a pH-dependant characteristic. The modeling data indicated that the release kinetics of insulin was nonlinear, and during the release process, the nanoparticles showed a polynomial swelling. On overall estimation, the insulin chitosan-Eudragit L100-55 nanoparticles may be better for the oral delivery. This new pH-sensitive nanoparticle formulation using chitosan and Eudragit L100-55 polymer may provide a useful approach for entrapment of hydrophilic polypeptides without affecting their conformation.     

Effect of Microsphere Size and Formulation Factors on Drug Release from Controlled-Release Furosemide Microspheres

Controlled-release furosemide microspheres were prepared with various combinations of Eudragit L: Eudragit RS and Eudragit S: Eudragit RS and release of drug from microspheres containing these polymers in different ratios was studied. A wide range of release rates of drug can obtained by a simple change in the ratio of polymers. An increase in Eudragit RS content of polymer microsphere matrix brought about a decrease in the release rate.

On the other hand, the effect of particle size on the drug release rate from furosemide microspheres was also investigated. The effect of microsphere sizes on release rate depends on the type of Eudragit. The decrease in release rates of small microspheres may be due to agglomerate formation. Dissolution data indicated that the release followed Higuchi's matrix model kinetics.     

Preparation of the traditional Chinese medicine compound recipe heart-protecting musk pH-dependent gradient-release pellets

In this study a sustained-release formulation of traditional Chinese medicine compound recipe (TCMCR) was developed by selecting heart-protecting musk pills (HPMP) as the model drug. Heart-protecting musk pellets were prepared with the refined medicinal materials contained in the recipe of HPMP. Two kinds of coated pellets were prepared by using pH-dependent methacrylic acid as film-forming material, which could dissolve under different pH values in accordance with the physiological range of human gastrointestinal tract (GIT). The pellets coated with Eudragit L30D-55, which dissolves at pH value over 5.5, were designed to disintegrate and release drug in the duodenum. The pellets coated with Eudragit L100-Eudragit S100 combinations in the ratio of 1:5, which dissolve at pH value 6.8 or above, were designed to disintegrate and release drug in the jejunum to ileum. The pellets coated with HPMC, which dissolves in water at any pH value, were designed to disintegrate and release drug in the stomach. Finally, the heart-protecting musk sustained-release capsules (HPMSRC) with a pH-dependent gradient-release pattern were prepared by encapsulating the above three kinds of coated pellets at a certain ratio in hard gelatin capsule. The results of dissolution of borneol (one of the active compounds of the TCMCR) in vitro demonstrated that the coating load and the pH value of the dissolution medium had little effect on the release rate of borneol from pellets coated with hydroxypropyl methyl cellulose (HPMC), but had a significant effect on the release rate of borneol from pellets coated with Eudragit L30D-55 or Eudragit L100-Eudragit S100 combinations in the ratio of 1:5. The pellets coated with Eudragit L30D-55 at 30% (w/w) coating load or above had little drug release in 0.1 mol/L HCl for 3 hr and started to release drug at pH value over 5.5. The pellets coated with Eudragit L100-Eudragit S100 combinations in the ratio of 1:5 at 36% (w/w) coating load or higher had little drug release in 0.1 mol/L HCl for 3 hr and in phosphate buffer of pH value 6.6 for 2 hr, and started to release drug at pH value 6.8 or above. The release profiles of lipophilic bornoel and hydrophilic total ginsenoside from HPMSRC, consisting of three kinds of pellets respectively coated at a certain ratio with HPMC, Eudragit L30D-55, and Eudragit L100-Eudragit S100 in the ratio of 1:5, showed a characteristic of pH-dependent gradient release under the simulated gastrointestinal pH conditions and no significant difference between them. The results indicated that various components with extremely different physicochemical properties in the pH-dependent gradient-release delivery system of TCMCR could release synchronously while sustained-releasing. This complies with the organic whole concept of compound compatibility of TCMCR.     

Preparation of novel cationic copolymer microspheres and evaluation of their function by in vitro and in vivo tests as pH-sensitive drug carrier systems

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior whenthe pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.     

Effective Intestinal Absorption of Insulin in Diabetic Rats Using Enteric Coated Capsules Containing Sodium Salicylate

Abstract

The absorption of insulin manifested as percent reduction of blood glucose was evaluated after placement of capsules containing 4.6 units of the drug and 20 mg of Sodium salicylate as an absorption promoter in the rate stomach. The capsules were coated with either Eudragit L100 or Eudragit 9100 to deliver insulin in different regions of small intestine of the rats as they are pH dependent. The data obtained after administration of the capsules were compared with that after intraperitoneal injection of 1 U of insulin and ALSO after administration of coated capsules containing insulin alone. The administration of insulin capsules containing sodium salicylate result in a significant (p<0.01) increase of the hypoglycemic effect over the 5 h period of the experiments. They produced the same hypoglycemia effect as I.P. injection at 5 h point. The areas under the % blood glucose reduction curves produced were 363.5, 221.7 and 236.5% h for I.P. injection and capsules coated with Eudragit L100 and Eudragit S100, respectively. The relative bioavailabilities of capsules to I.P. injection were 13.26 and 14.15% for those coated with Eudragit L100 and Eudragit S100, respectively. Enteric coated capsules of insulin alone caused no glucose reduction.     

Multiparticulate drug delivery system of aceclofenac: development and in vitro studies

The aim of this study was to develop an enteric-coated multiunit dosage form containing aceclofenac, a nonsteroidal anti-inflammatory drug. The pellets were prepared by using extrusion/spheronization method, and the core pellets were coated with a pH-sensitive poly(meth) acrylate copolymer (Eudragit L100-55) to achieve site-specific drug release. The formulated pellets were characterized for percentage yield, size distribution, surface morphology studies, drug content, and flow properties. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets. The practical yield was found to be 90-95%. The particle size of enteric-coated pellets was found to be in the range of 0.59-0.71 mm. The pellets were spherical in shape and surfaces of pellets were found to be rough and showing micropores. Enteric-coated pellets showed good flow properties and in vitro dissolution profile. Dissolution tests were carried out in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The release of the aceclofenac from formulated pellets was established to be minimum in the pH 1.2 (<5%) for a period of 2 h, and at pH 6.8, it shows the maximum release (85 +/- 5% release within 1 h) which indicates gastric resistance of the formulated pellets. The 20% wt/wt enteric-coated pellets were compared to that of marketed product (tablets), it was observed that pellets showed better release profile. The study concluded that the formulated multiparticulate dosage forms can be used as an ideal drug delivery system for the aceclofenac.