Hydroxypropyl Methylcellulose Capsules Research Articles

Effect of hydroxypropyl methylcellulose (HPMC) hard capsules on in vitro rumen fermentation kinetics of commonly used feeds in ruminant feeding.

Accurate dosing of feed additives is often required to evaluate their effects on rumen fermentation. This can be done using soluble but nonfermentable hydroxypropyl methylcellulose (HPMC) hard capsules. The aim of the study was to evaluate the effect of HPMC hard capsules on the extent and rate of in vitro gas production in eleven feeds. Six high-fibre feeds and five concentrates, were weighed into syringes either directly or into HPMC capsules and incubated anaerobically in 30mL buffered rumen fluid at 39°C. Data obtained from gas production measurements were fitted using the Gompertz model to obtain kinetic parameters for gas production. HPMC hard capsules had no effect on the gas production of the blank sample and concentrate feeds. In contrast, high-fibre feeds weighed in HPMC showed a significant decrease (p < 0.05) in total gas production and gas produced within 24 h of incubation. The use of HPMC hard capsules was found to be inappropriate for determining gas production kinetics because fermentation subsides at a certain point when peak fermentation is reached (at TMFR), resulting in a decrease in both total potential gas production and gas production within 24 h of incubation. This is particularly evident when high-fibre feeds are incubated.

PH-Sensitive Acrylic Terpolymers for the Coating of Orally Administered Drugs Used for Colonic Release.

Polymeric coatings are a promising option for the development of delivery systems for orally administered drugs. However, the gastrointestinal conditions to which they are subjected, which include low pH and solubility as well as peristaltic movements, can limit their applications. In this work, different formulations of polymeric coatings were produced using pH-sensitive materials consisting of copolymers of methyl acrylate, methyl methacrylate, and methacrylic acid. The polymers were synthesized by the emulsion polymerization technique, obtaining small average particle sizes (56-190 nm), molecular weights between 200,000 and 400,000 g/mol, and a glass transition temperature above 35 °C, which are suitable for film formation at room temperature. Thus, they were assessed as coatings for hydroxypropyl methylcellulose capsules (HPMC) using the immersion method, showing adequate capacity to protect the capsule at gastric pH (pH 1.2) and dissolve at the simulated intestinal pH (pH= 7.2). In particular, the higher the content of the acidic monomer, the higher the release time of the test molecule contained in the acrylic terpolymer-coated HPMC capsules proposed, which was a curcuminoid derivative due to their bright color and potential medical benefits. In addition, a minimum number of immersions was required for coating the HPMC capsules at high acidic concentrations, which further facilitates the delayed release needed for colonic treatment. However, too high proportions of methacrylic acid may result in cytotoxicity issues. Consequently, a biocompatible formulation containing a proportion of methyl acrylate, methyl methacrylate, and methacrylic acid of 7:3:3 is proposed as the most adequate for colonic release. Thus, by chemically modulating the molar percentages of the acrylic monomers, it was possible to obtain tailored acrylic terpolymer coatings with different characteristics and desired properties in order to modulate the release kinetics of an active substance in a colonic environment.

Near-infrared imaging of in vivo performance of orally administered solid forms to rats: Feasibility study with indocyanine green

This study demonstrates the applicability of near-infrared (NIR) imaging to evaluating in vivo oral formulation performance. As a NIR probe and model drug, indocyanine green (ICG) and acetaminophen (ACE) were selected, respectively. The fluorescence intensity of ICG greatly increased upon dissolution, with the dissolved ICG passing through the gastrointestinal tract over time. Both compounds (0.05 mg of ICG and 0.5 mg of ACE) were encapsulated in gelatin and hydroxypropyl methylcellulose (HPMC) capsules in the solid form. In vitro, the HPMC capsules showed a disintegration lag time, a feature that was not observed for the gelatin capsules. After oral administration of each capsule to rats, blood samples were collected, followed by fluorescent imaging of the abdominal region. At 0.25 h after HPMC capsule administration, the fluorescence area and intensity were significantly small and relatively weak compared to that of the gelatin capsule. These tendencies resulted from the difference in capsule disintegration times, leading to a change in gastric emptying, which corresponded well with the initial time profile of the plasma concentration of ACE. These results indicate that possibility of NIR imaging with ICG to evaluate in vivo performance of orally administered formulations.

Delayed Release HPMC Capsules for Efficient Delivery of Cholecalciferol Solid Dispersion

Abstract: Introduction: The deficiency of Vitamin D is associated with an increased risk of various diseases and deficiency of this Vitamin is recognized in individuals all over the world. Therefore, the intake of Vitamin D has become essential. Objectives: Cholecalciferol (Vitamin D3) is a poorly soluble molecule and it is very sensitive to degradation under environmental factors such as light, temperature, and oxygen. Its stability is also affected adversely under acidic conditions. Therefore, solid dispersion-based formulation for cholecalciferol was developed and encapsulated in delayed release hydroxypropylmethyl cellulose (HPMC) capsules. Materials and Methods: Cholecalciferol solid dispersion was developed and characterized by Fourier transform–infra red spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction analysis. The effect of various concentrations of cholecalciferol formulations on the viability of Caco-2 cells was determined by using MTT assay. Dissolution profile and stability study of the developed product was also evaluated. Results: The results demonstrated improved solubility of cholecalciferol in solid dispersion-based formulation. The drug content of solid dispersions was in the order of 91±2.3% and various studies showed the amorphous form of cholecalciferol in the solid dispersion. The cell viability assay in Caco-2 cells demonstrated that the surfactant used in the solid dispersion formulation of cholecalciferol had no adverse effect on intestinal cells. Further, dissolution profile of HPMC capsule encapsulated solid dispersion showed improved dissolution of cholecalciferol. Moreover, the stability study indicated no significant changes in the cholecalciferol content in the developed formulation under storage at experimental conditions. Conclusion: The solid dispersion-based formulation of cholecalciferol exhibited improved solubility and found to be compatible with Caco-2 cells. The delayed release HPMC capsule encapsulated solid dispersion of cholecalciferol (DRHCap-SD) showed improved dissolution and acceptable stability profile and this represent a potential delivery system for oral administration of cholecalciferol. Keywords: Solid dispersion, Cholecalciferol, HPMC capsule, Caco-2 cells, Oral delivery, Dissolution.

Application of electrostatic dry powder coating technology on capsules to achieve sustained release

This study introduces an electrostatic dry powder coating process to coat hard gelatin capsules and hydroxypropyl methylcellulose capsules directly in a coating pan to achieve sustained release. The process overcomes many difficulties in the capsule liquid coating process, such as stickiness and poor adhesion. According to the results of SEM, the coating process required more polymer powder to seal the weakest area of the capsule, the joint of the body and the cap. The dissolution test showed that various release rates were achieved successfully by adjusting the formulations of coating materials and the weight gain of capsules. The capsule shell would also influence the drug release rate due to the dissolubility of capsule materials. This study demonstrates that electrostatic dry powder coating technology can be applied on hard HPMC capsules and gelatin capsules to achieve sustained release of the capsules. Aspirin and caffeine were used as the active pharmaceutical ingredients. • Electrostatic dry powder coating technology was successfully applied on capsules. • Hard gelatin and HPMC capsules were coated to achieve sustained release. • Minimum weight gain is required to prevent leakage from the capsule gap. • Ratio and concentration of Eudragit RS, RL can control release rate of capsules. • Capsule materials influence the release behavior of the coated capsules.

Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis.

Commercially available hydroxypropyl methylcellulose capsules are employed as a fast, safe, and user-friendly chemical delivery system containing all reagents (catalyst, ligand, and base) for three important transition-metal-catalyzed reactions: Buchwald-Hartwig, Suzuki-Miyaura, and metallophotoredox C-N cross-coupling reactions. This encapsulation methodology simplifies the screening of reaction conditions and the preparation of compound libraries using parallel synthesis in organic solvents or aqueous media. These reagents-containing HPMC capsules are easy to prepare, come in different sizes, and can be stored on the bench under noninert conditions.

Suitability of phosphatidylcholine-based formulations for liquid filling in hard capsules

The current study aimed to evaluate whether phosphatidylcholine-based formulations have suitable properties for liquid filling in hard capsules. Liquid or semisolid formulations were obtained with Miglyol 812 (medium chain triglycerides) or Softisan 378 (semisolid hard fat), respectively, in combination with three different phospholipids (Phospholipon 90 G, Lipoid S 75 or Lipoid S LPC 80) and ethanol. Suitability for the filling process was evaluated by rheological characterization and stringing tests. Liquid and semisolid mixtures with Lipoid S 75 or Phospholipon 90 G (also with addition of Lipoid S LPC 80) exhibited appropriate viscosity at the respective filling temperatures. Liquid mixtures with up to 60% Phospholipon 90 G broke cleanly from the needle during filling simulations. A higher fraction of phospholipid led to stringing which could be reduced by addition of ethanol. The hygroscopicity of the formulations was investigated as was their compatibility with different capsule materials with regard to their impact on capsule brittleness and integrity. Gelatin capsules became brittle due to the hygroscopic properties of phosphatidylcholine-based mixtures whereas hydroxypropyl methylcellulose capsules were compatible with a wide range of formulations. After aeration with nitrogen, the formulations exhibited acceptable stability against oxidation.

Moisture sorption and desorption properties of gelatin, HPMC and pullulan hard capsules

The moisture sorption and desorption properties of hard capsules have a great influence on the quality of capsule products. However, studies on them have rarely been reported. Herein, we studied the moisture sorption and desorption properties of three kinds of hard capsules (gelatin, hydroxypropyl methyl cellulose (HPMC) and pullulan capsules) in terms of hygroscopicity, crystallinity, thermal behaviors and so on. It is found that HPMC capsules have weaker moisture sorption ability and moisture keeping ability than pullulan or gelatin capsules with lower moisture sorption rates, equilibrium moisture contents, moisture keeping rates and higher critical relative humidity. In comparison with gelatin capsules, pullulan capsules have weaker moisture sorption ability and comparable moisture keeping ability. HPMC or pullulan capsules can more effectively protect high, moderate and low hygroscopic capsule contents (chitosan, potato starch or ethyl cellulose) from outside moisture absorption. The diffraction peaks of the moisture equilibrated gelatin, HPMC and pullulan capsules are much smaller than those of their dried ones. The dried and the moisture equilibrated gelatin, HPMC or pullulan capsules all have smooth surface morphology. HPMC or pullulan capsules can be an attractive alternative to animal gelatin capsules due to their appropriate moisture sorption and desorption properties.

Evaluation of the Physico-mechanical Properties and Electrostatic Charging Behavior of Different Capsule Types for Inhalation Under Distinct Environmental Conditions

Capsule-based dry powder inhaler (DPI) products can be influenced by a multitude of interacting factors, including electrostatic charging. Tribo-charging is a process of charge transfer impacted by various factors, i.e., material surface characteristics, mechanical properties, processing parameters and environmental conditions. Consequently, this work aimed to assess how the charging behavior of capsules intended for inhalation might be influenced by environmental conditions. Capsules having different chemical compositions (gelatin and hydroxypropyl methylcellulose (HPMC)) and distinct inherent characteristics from manufacturing (thermally and cold-gelled) were exposed to various environmental conditions (11%, 22% and 51% RH). Their resulting properties were characterized and tribo-charging behavior was measured against stainless steel and PVC. It was observed that all capsule materials tended to charge to a higher extent when in contact with PVC. The tribo-charging of the thermally gelled HPMC capsules (Vcaps® Plus) was more similar to the gelatin capsules (Quali-G™-I) than to their HPMC cold-gelled counterparts (Quali-V®-I). The sorption of water by the capsules at different relative humidities notably impacted their properties and tribo-charging behavior. Different interactions between the tested materials and water molecules were identified and are proposed to be the driver of distinct charging behaviors. Finally, we showed that depending on the capsule types, distinct environmental conditions are necessary to mitigate charging and assure optimal behavior of the capsules.

Intravaginal administration of progesterone using a new technique for sustained drug release in goats.

The objective of the present study was to develop and evaluate a sustained release vaginal progesterone (P4) capsule containing a mixture of mucoadhesive polymer and silicone fluid. Goats were administered a gelatin capsule containing 0.4 g of P4 mixed in silicone fluid and either a hydroxypropylmethylcellulose (HM) or polyaclil starch (PA) base. The mean plasma P4 concentrations at 2 and 12 h after administration were significantly higher in goats treated with PA capsules than in those with HM capsules. The plasma P4 concentrations in goats treated with HM capsules increased and remained above 1.0 ng/ml for 96 h after administration, whereas the plasma P4 concentrations in goats treated with PA capsules remained above 1.0 ng/ml for only 24 h after administration. In the next experiment, an HM capsule was attached to a silicone device and inserted in the vagina for 10 days. The plasma P4 concentration remained similar to that of the natural luteal phase for 9 days. These results suggest that a mixture of mucoadhesive polymer and silicone fluid has the potential to be applied clinically as a sustained release base for estrus synchronization or hormonal therapy.

HPMC AS CAPSULE SHELL MATERIAL: PHYSICOCHEMICAL, PHARMACEUTICAL AND BIOPHARMACEUTICAL PROPERTIES

The most common instability problem of gelatin capsules arises from negative impact of extremes of temperature and especially atmospheric relative humidity on the mechanical integrity of the capsule shells with adverse effect extended even to the fill material. Moreover, choice of fill materials is highly restricted either due to their specific chemical structure, physical state or hygroscopicity. Additional reports of unpredictable disintegration and dissolution of filled hard gelatin capsules in experimental studies have prompted the search for a better alternative capsule shell material. The present review aims to provide an overview on the physicochemical, pharmaceutical and biopharmaceutical properties of hydroxypropyl methylcellulose (HPMC) as capsule shell material and perform comparative evaluation of HPMC and gelatin in terms of in vitro/in vivo performance and storage stability. HPMC capsule provides a highly flexible and widely acceptable platform capable of solving numerous challenges currently facing the pharmaceutical and nutraceutical industries and expands the possibilities for selection of different types of fill materials. The current topic introduces a new section on influence of various factors on in vitro dissolution of HPMC capsules. Delayed in vitro disintegration/dissolution of HPMC capsules in aqueous medium does not produce any negative effect in vivo. However, advancements in the processes of production and filling of HPMC capsule shells and detailed studies on effects of various parameters on their in vitro/in vivo dissolution would establish their supremacy over hard gelatin capsules in future.

Drug release behavior of polymeric matrix filled in capsule

A single unit sustainable drug release system was developed using hydroxypropyl methylcellulose (HPMC)-based matrices filled in capsule as the drug delivery device. Release behavior of propranolol HCl from these capsules was investigated and least square fitting was performed for the dissolution data with the different mathematical expressions. Effect of diluent, polymer, pH and hydrodynamic force on the drug release from the developed systems was investigated. The utilization of HPMC as a matrix former extended the drug release longer than 8h. HPMC viscosity grades affected the drug release, that is, increasing the amount of fillers such as lactose and dibasic calcium phosphate enhanced the drug release rate of HPMC matrices. The hydrodynamic force, type and amount of incorporated polymer apparently influenced the drug release. The physiochemical properties of polymers and interaction between HPMC and other polymers were important factors for prolongation of the drug release. The release mechanism from HPMC-based matrices in capsules was the non-Fickian transport in which the sustainable drug release of HPMC capsules could be achieved by the addition of polymeric matrix.

Factorial designed 5-fluorouracil-loaded microsponges and calcium pectinate beads plugged in hydroxypropyl methylcellulose capsules for colorectal cancer.

Introduction:The work was aimed to develop an enteric-coated hydroxypropyl methylcellulose (HPMC) capsules (ECHC) plugged with 5-fluorouracil (5-FU)-loaded microsponges in combination with calcium pectinate beads.Materials and Methods:The modified quasi-emulsion solvent diffusion method was used to prepare microsponges. A 32 factorial design was employed to study the formulation and the effects of independent variables (volume of organic solvent and Eudragit-RS100 content) on dependent variables (particle size, %entrapment efficiency, and %cumulative drug release). The optimized microsponge (F4) was characterized by scanning electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. F4 was plugged along with the calcium pectinate beads in HPMC capsules coated with enteric polymer Eudragit-L100 (Ed-L100) and/or Eudragit-S100 (Ed-S100) in different proportions. An in vitro release study of ECHC was performed in simulated gastric fluid for 2 h, followed by simulated intestinal fluid for next 6 h and then in simulated colonic fluid (in the presence and absence of pectinase enzyme for further 16 h). The optimized formulation was subjected to in vivo roentgenographic and pharmacokinetic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon-targeted capsules.Results:Drug release was retarded on coating with Ed-S100 in comparison to a blend of Ed-S100:Ed-L100 coating. The percentage of 5-FU released at the end of 24 h from ECHC3 was 97.83 ± 0.12% in the presence of pectinase whereas in the control study, it was 40.08 ± 0.02%.Conclusion:Thus, enteric-coated HPMC capsules plugged with 5-FU-loaded microsponges and calcium pectinate beads proved to be a promising dosage form for colon targeting.

Moisture diffusion and permeability characteristics of hydroxypropylmethylcellulose and hard gelatin capsules

The primary objective of this paper is to compare the sorption characteristics of hydroxypropylmethylcellulose (HPMC) and hard gelatin (HG) capsules and their ability to protect capsule contents. Moisture sorption and desorption isotherms for empty HPMC and HG capsules have been investigated using dynamic vapour sorption (DVS) at 25°C. All sorption studies were analysed using the Young–Nelson model equations which distinguishes three moisture sorption types: monolayer adsorption moisture, condensation and absorption. Water vapour diffusion coefficients (D), solubility (S) and permeability (P) parameters of the capsule shells were calculated. ANOVA was performed with the Tukey comparison test to analyse the effect of %RH and capsule type on S, P, and D parameters. The moisture uptake of HG capsules were higher than HPMC capsules at all %RH conditions studied. It was found that values of D and P across HPMC capsules were greater than for HG capsules at 0–40 %RH; whereas over the same %RH range S values were higher for HG than for HPMC capsules. S values decreased gradually as the %RH was increased up to 60% RH. To probe the effect of moisture ingress, spray dried lactose was loaded into capsules. Phase evolution was characterised by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The capsules under investigation are not capable of protecting spray dried lactose from induced solid state changes as a result of moisture uptake. For somewhat less moisture sensitive formulations, HPMC would appear to be a better choice than HG in terms of protection of moisture induced deterioration.

Effects of particle size, food, and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors

Dabrafenib is a small-molecule inhibitor of BRAF kinase activity that is currently being developed for the treatment of BRAF V600 mutation-positive melanoma. This clinical, open-label, two-cohort (n = 14 per cohort), randomized study was designed to evaluate the effect of drug substance particle size, and food on the plasma pharmacokinetics of a single oral dose of dabrafenib in patients with BRAF V600 mutation-positive solid tumors. In addition, an exploratory cross-cohort comparison of the relative bioavailability of single-dose dabrafenib administered in gelatin and hydroxypropyl methylcellulose (HPMC) capsules was performed. Higher bioavailability was noted with nonmicronized drug substance (larger particle size), under fasting conditions, and with HPMC capsules. Initial dissolution results at pH 1.2 showed higher dissolution of gelatin relative to HPMC capsules inconsistent with clinical data. Subsequent in vitro dissolution studies were conducted in fasted-state simulated gastric fluid over a 24-h period and showed that HPMC capsules reached a higher percentage of dabrafenib dissolved than gelatin capsules. The presence of HPMC is believed to inhibit precipitation of dabrafenib as the freebase, thereby maintaining a supersaturated solution over an extended period of time. Dabrafenib has been administered in pivotal clinical studies on an empty stomach using micronized drug substance in HPMC capsules. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3100–3109, 2013

Efficacy, safety, and pharmacokinetics (PK) of the BRAF inhibitor dabrafenib (D) hydroxypropyl methylcellulose (HPMC) capsule formulation in combination with the MEK1/2 inhibitor trametinib (T) in patients (pts) with BRAF mutation-positive metastatic melanoma (MM).

9066 Background: Preclinical studies ofD + T show enhanced activity in BRAF mutant MM vs either drug alone. D + T safety and efficacy were evaluated in a 4-part (A–D) phase I/II study. Part D assessed the impact on efficacy, safety and PK of a more stable HPMC capsule formulation of D alone, and in combination with T, instead of the gelatin capsule used in Parts A–C. Methods: 110BRAFV600E/KMM pts with RECIST measurable disease were randomized to 4 cohorts. Dose-limiting toxicities (DLTs) were evaluated for the first 3 weeks of treatment. PK sampling was done on Days 1 and 21. Primary endpoints were PK and safety; secondary endpoints were response rate (RR) and overall survival (OS). Results: Median age was 54 years, 58% male, 65% ECOG PS 0, 88% V600E, 68% M1c stage, 97% no prior brain metastases, and 45% LDH &gt; ULN. Treatment (tx) with D HPMC + T had little impact on ratio of D Cmax (1.16) and D AUC (1.23) vs D tx alone; but led to higher ratio of D Cmax(1.51) but similar D AUC (1.10) vs D gelatin + T seen in Part B. Median progression-free survival (PFS) and RR are in Table. Median PFS not reached in D4. No DLTs occurred in the first 15 subjects enrolled in D4. Most common AEs (≥40%) for all cohorts were pyrexia, nausea, chills, vomiting, arthralgia, and fatigue. Most common grade &gt;3 AEs (all 5%) were hypertension, pyrexia, increased GGT, and hyponatremia. 11% of pts discontinued treatment due to an AE. There were no major differences in toxicities between cohorts and Parts A–C. Conclusions: The D + T combination had an acceptable safety profile with clinically manageable side effects. D HPMC + T had little impact on D Cmax and D AUC vs D alone. D HPMC led to higher D Cmaxbut similar D AUC vs gelatin + T. Meaningful clinical activity was seen in all dose combinations with D HPMC +T; PFS, RR, and duration of response were consistent with other study parts. Phase 3 studies with D HPMC + T are ongoing. Clinical trial information: NCT01072175. [Table: see text]

Effect of aminoalkyl methacrylate copolymer E/ HCl on in vivo absorption of poorly water-soluble drug

This study aimed to investigate in vivo absorption of tacrolimus formulated as a solid dispersion using Eudragit E®/HCl (E-SD). E-SD is an aminoalkyl methacrylate copolymer that can be dissolved under neutral pH conditions. E-SD was used alone as a solid dispersion carrier and/or was mixed with tacrolimus primarily dispersed with hydroxypropylmethylcellulose (HPMC). Tacrolimus was formulated with E-SD at several different ratios. Formulations with tacrolimus/E-SD ratio of 1/3 showed higher in vivo absorption, compared to tacrolimus dispersed in the excipients (primarily HPMC) found in commercially available tacrolimus capsules, using a rat in situ closed loop method. Good correlation was observed between in vitro drug solubility and in vivo drug absorption. In vitro solubility tests and rat oral absorption studies of tacrolimus/HPMC solid dispersion formulations were also conducted after mixing the HPMC dispersion with several ratios of E-SD. E-SD/tacrolimus/HPMC formulations yielded high in vitro drug solubility but comparatively low in vivo absorption. Dog oral absorption studies were conducted using capsules containing a formulation of tacrolimus/E-SD at a ratio of 1/5. The E-SD formulation-containing capsule showed higher in vivo drug absorption than tacrolimus dispersed in the standard HPMC capsule. These studies report enhancement of the in vivo absorption of a poorly water-soluble drug following dispersion with E-SD when compared to formulation in HPMC.

Development of Budesonide Nanocluster Dry Powder Aerosols: Formulation and Stability

The physical and chemical stability of dry powder aerosol formulations is an essential component in the development of an inhaled therapeutic. The pharmaceutical processing methods and storage conditions are primary determinants of the stability of a dry powder inhaler (DPI) formulation. Wet milling was used to produce budesonide NanoClusters (NCs), which are agglomerates of drug nanoparticles (≈ 300 nm) with a mean aerodynamic diameter between 1 and 3 µm, capable of deep lung penetration. In this study, the reproducibility of NC processing and performance was established. The physical stability of a selected budesonide NC formulation was investigated using industry standard dose content uniformity and cascade impaction techniques. The chemical stability of the lead formulation was also determined as a function of processing parameters and storage conditions. This study confirms the reproducibility and robust stability of NC powders as a novel means to turn drug particles into high-performance aerosols.

Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease

Objective: The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre-programmed time intervals.Methods: The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit® E100 and Eudragit® RS100.Results: In vitro evaluation of tablets coated with Eudragit® E100 and Eudragit® RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit® E100 from the Eudragit® E100 and Eudragit® RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit® L100 and Eudragit® S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit® L100 and Eudragit® S100, respectively.Conclusion: The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease.

Evaluation of hard gelatin capsules and hydroxypropyl methylcellulose containing ampicillin

This study aims to develop and evaluate formulations containing ampicillin in capsules of gelatin and hydroxypropyl methylcellulose (HPMC). Two formulations (A and B) were developed. The final product quality was evaluated by testing for quality control and the results were in agreement with the Brazilian Pharmacopoeia. The formulations with HPMC capsules showed lower percentages of drug dissolved (99.67%, HPMC-A and 87.70%, HPMC-B) than the gelatin (100.18%, GEL-A and 101.16% GEL-B). Because of the delay of the ampicillin release observed in the dissolution profiles, it becomes necessary to evaluate the drugs that can be conditioned in the HPMC capsules.