A novel natural GRAS-grade enteric coating for pharmaceutical and nutraceutical products.

In this study, enteric coatings based exclusively on naturally occurring ingredients were reported. Alginate (Alg) and pectin (Pec) blends with or without naturally occurring glyceride, glycerol monostearate (GMS), were initially used to produce solvent-casted films. Incorporating GMS in the natural polymeric films significantly enhanced the acid-resistance properties in gastric medium. Theophylline tablets coated with Alg-Pec blends without GMS disintegrated shortly after incubation in gastric medium (pH 1.2), leading to a premature and complete release of theophylline. Interestingly, tablets coated with Alg-Pec blends that contain the natural glyceride (GMS) resisted the gastric environment for 2 h with minimal drug release (<5%) and disintegrated rapidly following introduction to the intestinal medium, allowing a fast and complete drug release. Furthermore, the coating system proved to be stable for six months under accelerated conditions. These findings are particularly appealing to nutraceutical industry as they provide the foundation to produce naturally-occurring GRAS based enteric coatings.

Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions.

Diagnostic ion filtering strategy for chemical characterization of Guge Fengtong Tablet with high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

The present study was designed to characterize the chemical constituents of Guge Fengtong Tablet (GGFTT). Based on the chromatographic retention behavior, fragmentation pathways of chemical components and the published literatures, a diagnostic ion filtering strategy with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) was established to identify the multiple bioactive constituents of GGFTT. The rapid identification of forty-seven components, including 18 phenolic acids, 8 saponins, 14 gingerol-related compounds, and 7 diarylhepatonoids, was accomplished using this newly developed method. The coupling of HPLC-ESI-Q-TOF/MS with the diagnostic ion filtering strategy was useful and efficient for the in-depth structural elucidation of chemical compounds of GGFTT.

Preformulation studies for generic omeprazole magnesium enteric coated tablets.

Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr's index), Hauser's ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr's index 17.5%, Hauser's ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350-2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.

Evaluation of coating properties of enteric-coated tablets using terahertz pulsed imaging.

PURPOSE: Enteric coatings are used to reduce gastrointestinal side effects and control the release properties of oral medications. Although widely used, the effect of formulation and process conditions on physicochemical and functional properties of enteric coatings remains unclear. METHODS: Terahertz pulsed imaging (TPI) was employed to evaluate the coat properties of enteric coated tablets (ECTs) with various acid resistance. Other analytic methods, such as loss on drying, scanning electron microscopy and X-ray computed tomography were then used to validate the relationships established among 4 TPI-derived parameters and the physicochemical properties of enteric coatings. RESULTS: Weight gain measurement did not provide any information to assess acid resistance of enteric coating, whereas four TPI-derived parameters non-destructively reflected the coating properties such as thickness, coat uniformity, density, and water distribution, allowing the identification of the causes of poor acid resistance in certain ECT batches using a single measurement. These parameters also revealed the effect of coating conditions; in particular, coating under dry conditions led to less dense and nonuniform coatings with poor acid resistance. CONCLUSION: We demonstrated the utility of TPI to identify structural defects within ECTs with poor acid resistance. TPI-derived parameters can aid in formulation development and quality control of ECTs.

Novel method for screening of enteric film coatings properties with magnetic resonance imaging.

The aim of the study is to present the concept of novel method for fast screening of enteric coating compositions properties without the need of preparation of tablets batches for fluid bed coating. Proposed method involves evaluation of enteric coated model tablets in specially designed testing cell with application of MRI technique. The results obtained in the testing cell were compared with results of dissolution studies of mini-tablets coated in fluid bed apparatus. The method could be useful in early stage of formulation development for screening of film coating properties that will shorten and simplify the development works.

A two pulse drug delivery system for amoxicillin: an attempt to counter the scourge of bacterial resistance against antibiotics.

Bearing in mind the present scenario of the increasing biological tolerance of bacteria against antibiotics, a time controlled two pulse dosage form of amoxicillin was developed. The compression coating inlay tablet approach was used to deliver the drug in two pulses to different parts of the GIT after a well defined lag time between the two releases. This was made possible by formulating a core containing one of the two drug fractions (intended to be delivered as the second pulse), which was spray coated with a suspension of ethyl cellulose and a hydrophilic but water insoluble agent as a pore former (microcrystalline cellulose). Coating of up to 5% (m/m) was applied over the core tablet, giving a corresponding lag of 3, 5, 7 and 12 h. Increasing the level of coating led to retardation of the water uptake capacity of the core, leading to prolongation of the lag time. Microcrystalline cellulose was used as a hydrophilic but water insoluble porosity modifier in the barrier layer, varying the concentration of which had a significant effect on shortening or prolongation of the lag time. This coated system was further partially compression coated with the remaining drug fraction (to be released as the first immediate release pulse) with a disintegrant, giving a final tablet. The core tablet and the final two pulse inlay tablet were further investigated for their in vitro performance.

In vitro evaluation of compression-coated glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu2+)-loaded microparticles for colonic drug delivery.

Glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu(2+))-loaded Zn-pectinate microparticles in the form of hydroxypropyl cellulose (HPC) compression-coated tablets were prepared and their in vitro behavior tested. GHK-Cu(2+) delivery to colon can be useful for the inhibition of matrix metalloproteinase, with the increasing secretion of tissue inhibitors of metalloproteinases (TIMPS),which are the major factors contributing in mucosal ulceration and inflammation in inflammatory bowel disease. The concentration of peptide was determined spectrophotometrically. The results obtained implied that surfactant ratio had a significant effect on percent production yield (1.25 to 1.75 w/w; 72.22% to 80.84%), but cross-linking agent concentration had not. The entrapment efficiency (EE) was found to be in the range of 58.25-78.37%. The drug-loading factor significantly increased the EE; however, enhancement of cross-linking agent concentration decreased it. The release of GHK-Cu(2+) from Zn-pectinate microparticles (F1-F8) in simulated intestinal fluid was strongly affected by cross-linking agent concentration and drug amount (50 mg for F1-F6; 250 mg for F7-F8), but not particularly affected by surfactant amount. Release profiles represented that the microparticles released 50-80% their drug load within 4 h. Therefore, the optimum microparticle formulation (F8) coated with a relatively hydrophobic polymer HPC to get a suitable colonic delivery system. The optimum colonic delivery tablets prepared with 700 mg HPC-SL provided the expected delayed release with a lag time of 6 h. The effects of polymer viscosity and coat weight on GHK-Cu(2+) release were found to be crucial for the optimum delay of lag time. The invention was found to be promising for colonic delivery.

Preparation and in vitro evaluation of mebeverine HCl colon-targeted drug delivery system.

Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.

[Preparation of paeonol-beta-cyclodextrin inclusion complex loaded colon specific delivery tablets].

OBJECTIVE: To prepare paeonol-beta-cyclodextrin inclusion complex (Pae-beta-CYD) loaded colon-specific release tablets. METHOD: The core tablets were prepared with the mixture of Pae-beta-CYD inclusion complex, peotin and calcium acetate, and coated with ethanolic solution of Eudragit S100. The effects of coating weight, amount of plasticizer, curing time and temperature on the release of drug from tablets were investigated in vitro. RESULT: About 5-6 h retarded release of paeonol in the dissolution media of pectinase or rats colon contents were obtained by 12% coating weight gain and 20% Dibutyl phthalate (DBP) was used as plasticizer, and subsequently curing the tablets at 45 degrees C for 12 h. CONCLUSION: Pae-beta-CYD loaded colon-specific release tablets showed pH environment and enzyme dependant release properties.

Evaluation of recent advances in continuous film coating processes.

BACKGROUND: Continuous film coating processes are recognized for their high production rates but have had slow acceptance for pharmaceutical production because of perceived high product losses during start-up and shut-down. In this article, the recent improvements in continuous coater designs were evaluated with respect to coating uniformity and reduction in product losses. Two separate studies represent trials conducted in newly redesigned continuous coating pans from two different coating pan manufacturers. METHOD: Multivitamin tablets were coated with Opadry((R)) II, high performance film coating system, in both batch and continuous modes in the continuous coater. Tablet samples collected throughout all phases of the process were tested for color development and uniformity. Soft gelatin capsules were coated with a delayed release coating formulation, Nutrateric((R)), nutritional enteric coating system. Samples of the soft gelatin capsules were taken throughout the process and tested for resistance to simulated gastric fluid as a measure of coating uniformity and delayed release functionality performance. CONCLUSIONS: The results from both the immediate release and delayed release case studies support the assertion that continuous coating processes are capable of applying aqueous film coatings with significant improvements in coating uniformity and reduction in product loss.

[Preparation and prescription of enteric coated pellets of Panax notoginseng saponins pellets].

OBJECTIVE: To prepare enteric coated pellets containing panax notoginseng saponins. METHOD: Panax notoginseng saponins loaded pellets were prepared by Extrusion-Spheronization method, and coated by Eudragit L30D-55 using Glatt fluid bed with the bottom spray process, central composite design was used to optimize the coating prescription. RESULT: The drug release of enteric coated pellets of panax notoginseng saponins pellets would be lower than 5% in 2 h in simulated gastric fluid, but reach above 85% in 3 h in simulated human gastroenteric environment. CONCLUSION: The enteric coated pellets of panax notoginseng saponins have good acid residence to avoid panax notoginseng saponins from degrading in gastric acid.

[Preparation of gastric retenting and chronopharmacologic drug delivery tablets of sinomenine hydrochloride].

OBJECTIVE: To prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results. METHOD: The gastric retenting and chronopharmacologic drug delivery tablets were prepared by press-coated technics. The types of disintegrants were chosen according to the expanding rate and the lag-time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test. RESULT: The tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS-Na was selected as the disintegrant. The lag-time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag-time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release. CONCLUSION: The tablets had typical chronopharmacologic drug delivery properties. A suitable lag-time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.

Characterization of 5-fluorouracil microspheres for colonic delivery.

The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 microm, and the size of the coated microspheres ranged from 103 to 185 microm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1:7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40 degrees C/75% relative humidity for 6 months.

[Studies on using spray drying technique in preparing Ophiopogon japonicus saponin enteric microsphere by orthogonal experimental design].

OBJECTIVE: To explore the best technique parameters on preparing ophiopogon japonicus saponin enteric microsphere by spray drying technique. METHOD: The best technique parameters were investigated by orthogonal experimental design and by the target, such as surface appearances, encapsulated efficiency, etc. RESULT: The best technique parameters included the inlet temperature (90 degrees C ), the feeding speed (10 mL x min(- 1)), and the rotate speed of atomizer (50 r x min(-1)). CONCLUSION: Ophiopogon japonicus saponin enteric microsphere accorded with the expecting demand. The main influencing factor was inlet temperature . It is suitable to industrialize in preparing Traditional Chinese Medicine microsphere.

Application of an electronic nose system for evaluation of unpleasant odor in coated tablets.

The purpose of this study was to apply an electronic nose system for evaluation of unpleasant odor in tablets containing L-cysteine, an unpleasant odor drug, and demonstrate the odor masking ability of thin-layer sugarless coated tablets, which we have newly developed, by both electronic nose system and sensory evaluations. We demonstrated the qualitative evaluation of the unpleasant odor using air as a reference indicator and the quantitative evaluation of the unpleasant odor using the distances between air and samples in the electronic nose system evaluation. The electronic nose system evaluation was positively and well-correlated with the sensory evaluation by volunteers. We suggest that the electronic nose system evaluation is appropriate as an alternative or a support method for sensory evaluation by volunteers. As the results of both electronic nose system and sensory evaluations, we demonstrated that the thin-layer sugarless coated tablets have excellent masking ability of the unpleasant odor, equivalent to that of sugar-coated tablets due to the dense coating layers.

Formulation and evaluation of diclofenac sodium buccoadhesive discs.

Twenty diclofenac sodium buccoadhesive discs containing Cp974p, polycarbophil, PEO, SCMC-medium viscosity (SCMC-MV), SCMC-ultrahigh viscosity (SCMC-UHV) or their combinations were prepared. These buccoadhesive discs were evaluated for release pattern, swelling capacity, surface pH, mucoadhesion performance, and in vitro permeation of diclofenac sodium through buccal membranes. In vivo testing of mucoadhesion time, strength of adhesion, irritation, bitterness due to drug swallowing and disc disintegration in the buccal cavity were also performed. Drug bioavailability of a selected diclofenac sodium buccoadhesive product was then compared with that of Voltarin 100 SR tablet. The percentage relative bioavailability of diclofenac sodium from the selected buccoadhesive disc 50 mg was found to be 141.31%.

Modified guar gum matrix tablet for controlled release of diltiazem hydrochloride.

Polyacrylamide-grafted-guar gum (pAAm-g-GG) was prepared by taking three different ratios of guar gum to acrylamide (1:2, 1:3.5 and 1:5). Amide groups of these grafted copolymers were converted into carboxylic functional groups. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry were used to characterize copolymers. Tablets were prepared by incorporating an antihypertensive drug viz., diltiazem hydrochloride. In-vitro drug release was carried out in simulated gastric and intestinal conditions. Effect of drug loading on release kinetics was evaluated. Release continued up to 8 and 12 h, respectively, for pAAm-g-GG and hydrolyzed pAAm-g-GG copolymers. Nature of drug transport through the polymer matrices was studied by comparing with Higuchi, Hixson-Crowell and Kopcha equations. Drug release was found to be dissolution-controlled in case of unhydrolyzed copolymer. With hydrolyzed copolymers, drug release was swelling-controlled initially (i.e., in 0.1 N HCl), but at later stage, it became dissolution-controlled in pH 7.4. Hydrolyzed pAAm-g-GG matrices are pH sensitive and can be used for intestinal drug delivery.

Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release.

The gastrointestinal transit and in vivo drug release behaviour of a film-coated tablet formulation was investigated in five healthy human subjects using the technique of gamma scintigraphy. The film coating system consisted of a mixture of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a coat weight gain of 9%. The estimated mean values of the gastric emptying time (62+/-17 min), small intestinal transit time (219+/-53 min), ileocaecal junction lag time (79+/-30 min) and the colon arrival time (345+/-33 min), were similar to published values for the transit of similar sized tablets in humans. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach and the small intestine. There was increased release of radioactivity when the tablets were in the colon due to increased degradation of the film coatings by pectinolytic enzymes resident in the colon. The pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.