Capsule Disintegration Research Articles

The study of the diuretic activity and pharmacotechnological properties of a dry extract of Salvia sclarea L. growing in Tajikistan

Aim. To study the pharmacological activity of a dry extract of clary sage (DECS) growing in Tajikistan and its pharmacotechnological properties as basic stages in the development of the composition and technology of hard gelatin capsules with its content. Materials and methods. For the studies, we used DECS standardized by the content of the total amount of flavonoids and hydroxycinnamic acids. The quantitative content of the total amount of flavonoids was not less than 13.0 % calculated with reference to apigenin, and the quantitative content of the total amount of hydroxycinnamic acids was not less than 1.2 % calculated with reference to rosmarinic acid. The pharmacotechnological properties of DECS were studied according to methods of the State Pharmacopoeia of Ukraine (SPhU). Results and discussion. During screening, all doses of DECS studied showed a moderate diuretic activity. Thus, when using DECS in the dose of 100 mg/kg, the relative volume of the urine excreted by rats for 5 hours increased by 1.9 times, in the dose of 200 mg/kg – by 2.0 times, in the dose of 300 mg/kg – by 1.8 times compared to the same indicator in the negative control group (p˂0.05). When studying the complex of pharmacotechnological properties, it was found that DECS was a finely dispersed amorphous powder with particles of isodiametric form. DECS had an average bulk weight of 0.515 ± 0.002 g/mL, and the fluidity assessment showed that DECS had a very poor flowability, which value in the vibration mode of the device was 2.8 ± 0.1 g/s. According to the study of the fractional composition, DECS had a clearly expressed fine fraction with a particle size of less than 0.25-0.09 mm 84.68 %. Conclusions. Taking into account the results of the study of the diuretic activity and scientific literature data on the spectrum of the pharmacological activity of Salvia sclarea L, it is rational to consider DECS as a potential combined agent for enhancing the diuretic effect or in diseases of the urinary system accompanied by edema and inflammatory processes. The study of the pharmacotechnological indicators of DECS allows predicting the need to use certain groups of excipients to develop the composition and technology of capsules with its content, namely antifriction substances to improve fluidity and disintegrants to improve capsule disintegration, as well as substances that contribute to the compaction of bulk mass and moisture-regulating agents.

Flexible Coatings Facilitate pH-Targeted Drug Release via Self-Unfolding Foils: Applications for Oral Drug Delivery.

Ingestible self-configurable proximity-enabling devices have been developed as a non-invasive platform to improve the bioavailability of drug compounds via swellable or self-unfolding devices. Self-unfolding foils support unidirectional drug release in close proximity to the intestinal epithelium, the main drug absorption site following oral administration. The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules. The coated lid must remain intact to ensure drug protection in the rolled state until targeted release in the small intestine after capsule disintegration. Despite promising results in previous studies, the deposition of an enteric top coating that remains intact after rolling is still challenging. In this study, we compare different mixtures of enteric polymers and a plasticizer, PEG 6000, as potential coating materials. We evaluate mechanical properties as well as drug protection and targeted release in gastric and intestinal media, respectively. Commercially available Eudragit® FL30D-55 appears to be the most suitable material due to its high strain at failure and integrity after capsule fitting. In vitro studies of coated foils in gastric and intestinal media confirm successful pH-triggered drug release. This indicates the potential advantage of the selected material in the development of self-unfolding foils for oral drug delivery.

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.

In Vivo Evaluation of a Gastro-Resistant Enprotect® Capsule under Postprandial Conditions.

Ready-to-fill enteric hard capsule shells are an evolving field of oral drug and nutraceutical products. Lonza Capsugel® Enprotect® capsules were recently proven to provide reliable release in the small intestine after fasted intake, but robustness against postprandial intake needed to be proven. In this study, the capsules were administered to 16 healthy young subjects after intake of a light meal. The Enprotect® capsules were labelled with 5 mg black iron oxide and 25 mg 13C3-caffeine. Magnetic Resonance Imaging was used to identify the localization and visual dispersion of the capsule filling. The salivary appearance of caffeine was considered a second independent and sensitive marker for the initial release. Whereas the fasted gastric residence time of the capsules amounted to 43 ± 32 min, it was increased to 158 ± 36 min after postprandial intake. Therefore, the mean dispersion time according to MRI and the mean caffeine appearance time were increased to 196 ± 37 min and 189 ± 37 min, respectively. But, similar to fasted administration, no capsule disintegration or leakage was observed in the stomach and 38% of the capsules disintegrated in the jejunum and 62% in the ileum. The mean dispersion time after gastric emptying and the mean caffeine appearance time after gastric emptying amounted to 38 ± 21 min and 31 ± 17 min, respectively. Both did not relevantly change compared to the fasted intake. Only the absolute dispersion time and caffeine appearance were prolonged due to the increased gastric residence and no relevant influence of the light meal was observed on the disintegration or release behavior of Enprotect® capsules after gastric emptying. The capsules also showed robust enteric properties after postprandial administration.

Immediate-release dosage form; focus on disintegrants use as a promising excipient

Disintegrants are materials or mixtures of substances added in the drug formulations, which make easier dispersion or breakup of tablets and ingredients of capsules in small-scale particles for fast dissolution then it comes in contact with water in the GI tract. Immediate drug release dosage forms disintegrate rapidly after administration with an enhanced rate of dissolution. The superdisintegrants provide instantaneous disintegration of tablets after administration in the stomach. In this field, immediate-release liquid dosage forms and parenteral dosage forms have also been introduced for treating patients. The oral route is the most convenient route for the administration of solid dosage form, about 85% of solid dosage is administered by the oral route because of its advantages over others. The therapeutic activity of these formulations is obtained through a typical manner like disintegration followed by dissolution. Hence disintegration has a major role in facilitating drug activity. Diverse categories of superdisintegrants such as synthetic, semi-synthetic, natural, co-processed blends, multifunctional superdisintegrants, etc. have been employed to develop effectual orodispersible tablets and to overcome the limitations of conventional tablet dosage forms. The objective of the present review article is to highlight the various kinds of traditional, Natural crude drugs containing gum and mucilage, Co-processed, semisynthetic and synthetic disintegrants along with a concentration in tablet and capsule disintegration and effect on drug release, which are being used in the formulation to provide the safer, effective drug delivery with patient compliance. Also highlights the mechanism and use of disintegrants in the immediate release dosage form.
 Keywords: Disintegrants, Natural, Co-processed, Immediate release

Formulation and Biopharmaceutical Evaluation of Capsules Containing Freeze-Dried Cranberry Fruit Powder.

Cranberry fruits are an important source of anthocyanins and anthocyanidins. The aim of the present study was to investigate the effect of excipients on the solubility of cranberry anthocyanins and their dissolution kinetics as well as on the disintegration time of the capsules. Selected excipients (sodium carboxymethyl cellulose, beta-cyclodextrin and chitosan) were found to affect the solubility and release kinetics of anthocyanins in freeze-dried cranberry powder. Capsule formulations N1-N9 had a disintegration time of less than 10 min, and capsule formulation N10 containing 0.200 g of freeze-dried cranberry powder, 0.100 g of Prosolv (combination of microcrystalline cellulose and colloidal silicon dioxide), and 0.100 g of chitosan had a capsule disintegration time of over 30 min. The total amount of anthocyanins released into the acceptor medium ranged from 1.26 ± 0.06 mg to 1.56 ± 0.03 mg. Capsule dissolution test data showed that the time to release into the acceptor medium was statistically significantly longer for the chitosan-containing capsule formulations compared to the control capsules (p < 0.05). Freeze-dried cranberry fruit powder is a potential source of anthocyanin-rich dietary supplements, and the choice of excipient chitosan could be a suitable solution in capsule formulations providing greater anthocyanin stability and modified release in the gastrointestinal tract.

Formulation, Evaluation of Physical Properties, and In Vitro Antioxidant Activity Test of Moringa Leaf (Moringa oleifera L.) Ethanolic Extract Capsules

BACKGROUND: Supplements that contain antioxidants may enhance prevention and treatment effects of a wide range of diseases including COVID-19. Quercetin, a flavonoid compound, is a natural antioxidant that can neutralize free radicals. The current study was conducted to formulate Moringa leaf (Moringa oleifera L) ethanol extract capsules and to determine the quercetin antioxidant activity levels of Moringa ethanol extract capsule formulations. &#x0D; MATERIALS AND METHODS: We tested the total flavonoid levels in solutions with concentrations of 20, 50, 60, 70 and 100 ppm using Thin Layer Chromatography Densitometric method. Evaluation of physical properties of 96% Moringa leaf ethanol extract capsules included moisture content test, granule angle of repose test, granule flow property test, capsule weight uniformity test and capsule disintegration time test. Antioxidant activity test using the DPPH method with two samples, namely 96% Moringa leaf ethanol extract capsules with formulas I, II, III, quercetin as a comparison. &#x0D; RESULT: The results of the evaluation of 96% Moringa leaf ethanol extract capsules showed that formula II (PVP 50 mg) had good physical properties. Testing the antioxidant activity of capsules of ethanol extract of Moringa leaves formulas I, II, III, quercetin obtained IC50 values of 44.0 ppm, 40.2 ppm, 46.4 ppm, and 4.80 ppm, respectively. &#x0D; CONCLUSION: The evaluation of the ethanol extract capsules of Moringa leaf formula II, met the parameters of a good capsule evaluation test requirement and had very strong antioxidant activity seen from the acquisition of the IC50 value. The antioxidant properties of Moringa leaf extract capsules may be able to improve the immune system and clinical trials need to be carried out on patients to become candidates for prevention and therapeutic supplement fora range of diseases including COVID-19.

Transcriptional profiling of equine endometrium before, during and after capsule disintegration during normal pregnancy and after oxytocin-induced luteostasis in non-pregnant mares.

The current study used RNA sequencing to determine transcriptional profiles of equine endometrium collected 14, 22, and 28 days after ovulation from pregnant mares. In addition, the transcriptomes of endometrial samples obtained 20 days after ovulation from pregnant mares, and from non-pregnant mares which displayed and failed to display extended luteal function following the administration of oxytocin, were determined and compared in order to delineate genes whose expressions depend on the presence of the conceptus as opposed to elevated progesterone alone. A mere fifty-five transcripts were differentially expressed between samples collected from mares at Day 22 and Day 28 of pregnancy. This likely reflects the longer-term exposure to a relatively constant, progesterone-dominated environment with little change in factors secreted by the conceptus that would affect endometrial gene expression. The complement system was amongst the canonical pathways significantly enriched in transcripts differentially expressed between Day 14 and Day 22/28 of pregnancy. The expression of complement components 7 and 8 was confirmed using in situ hybridization. The expression of SERPING1, an inhibitor of the complement system, was confirmed by immunohistochemistry. In line with the resumed capacity of the endometrium to produce prostaglandin, prostaglandin G/H synthase 1 was expressed at higher levels at Days 22 and 28 than at Day 14 of pregnancy. Our data suggest that this up-regulation is enhanced by the presence of the conceptus; samples obtained from mares at Day 20 of pregnancy had significantly higher levels of prostaglandin G/H synthase 1 transcript than mares with extended luteal function.

Colonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: A clinical pharmacoscintigraphy study

Drug delivery to the colon offers great promise for local treatment of colonic diseases as it allows bypassing systemic absorption in the small intestine, thereby increasing luminal drug concentrations in the colon. The primary objective of this in vivo pharmaco-scintigraphy study was to assess the colon drug targeting accuracy of a metronidazole benzoate colonic drug delivery system intended for local treatment of Clostridioides difficile infections. Additionally, it was assessed if the concept of mucoadhesion would increase colonic residence time and promote higher drug bioavailability.Two different capsule formulations were designed and tested in healthy human subjects. Capsules contained either non-mucoadhesive (NM) or mucoadhesive (M) microgranules, both loaded with 100 mg metronidazole benzoate (antibiotic prodrug) and 5 mg samarium oxide (scintigraphy tracer). Filled capsules were coated with a colonic-targeting technology consisting of two functional layers, which allow for accelerated drug release mediated by the intestinal pH in combination with colonic bacteria. Coated capsules were neutron-activated to yield the radioisotope 153Sm prior to administration to 18 healthy subjects. Gamma-scintigraphy imaging was combined with the measurement of drug plasma levels.Formulation NM showed high colon-targeting accuracy. Initial capsule disintegration within the targeted ileocolonic region was observed in 8 out of 9 subjects (89%) with colonic arrival times in the range of 3.5–12 h and reduced systemic exposure. In contrast, the mucoadhesive formulation M showed some inconsistency regarding the site of initial capsule disintegration (targeting accuracy 56%). Variability of drug release was attributed to self-adhesion and agglomeration of the mucoadhesive microparticles within the capsule.Accurate ileocolonic delivery of metronidazole-loaded microgranules was achieved following oral administration of colonic-targeted capsules. Delayed drug release from NM microparticles in the colon leads to a reduced systemic exposure compared to immediate-release data from literature and presumably elevated drug concentrations in the colonic lumen. This approach offers promising options for the local treatment of colonic diseases.

Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing.

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice (p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.

Biopharmaceutical Evaluation of Capsules with Lyophilized Apple Powder.

Apples are an important source of biologically active compounds. Consequently, we decided to model hard gelatin capsules with lyophilized apple powder by using different excipients and to evaluate the release kinetics of phenolic compounds. The apple slices of “Ligol” cultivar were immediately frozen in a freezer (at −35°C) with air circulation and were lyophilized with a sublimator at the pressure of 0.01 mbar (condenser temperature, −85°C). Lyophilized apple powder was used as an active substance filled into hard gelatin capsules. We conducted capsule disintegration and dissolution tests to evaluate the quality of apple lyophilizate-containing capsules of different encapsulating content. Individual phenolic compounds can be arranged in the following descending order according to the amount released from the capsules of different compositions: chlorogenic acid > rutin > avicularin > hyperoside > phloridzin > quercitrin > (−)-epicatechin > isoquercitrin. Chlorogenic acid was the compound that was released in the highest amounts from capsules of different encapsulating content: its released amounts ranged from 68.4 to 640.3 μg/mL. According to the obtained data, when hypromellose content ranged from 29% to 41% of the capsule mass, the capsules disintegrated within less than 30 min, and such amounts of hypromellose did not prolong the release of phenolic compounds. Based on the results of the dissolution test, the capsules can be classified as fast-dissolving preparations, as more than 85% of the active substances were released within 30 min.

Novel Swellable/Expandable Gastroretentive Floating Films of Gliclazide Folded in Capsule Shell for the Effective Management of Diabetes Mellitus: Formulation Development, Optimization and In Vitro Evaluation

Background: Gliclazide (GLZ) belongs to the second-generation of sulphonylureas; it is a drug of choice for the management of type II DM. It belongs to BCS Class II. The major site of drug absorption for GLZ is the stomach; it displays variation in the drug absorption rate and bioavailability due to the shorter gastric retention time. The floating mechanism gets affected when the gastric fluid level is not sufficiently higher, which ultimately obstructs the floating behavior, which is the major limitation of reported formulations. This limitation can be overcome by folding the film into the capsule shell dissolved in the gastric fluid and the film swells/expands to dimensions higher than pylorus sphincter (12mm), thus preventing its evacuation. Objective: The study aims to explore the floating mechanism in the design of films along with a tendency to expand by swelling and unfolding by utilizing a mixture of hydrophilic and hydrophobic polymer to achieve the controlled drug delivery and prolonged gastric retention of drug. Methods: The gastroretentive floating films were formulated by the solvent casting technique using 32 full factorial designs and subjected to in vitro evaluation parameters, drug-excipient compatibility, Xray diffraction and accelerated stability study. Results: The pre-formulation study established the purity and identification of a drug. FTIR study confirmed no drug excipient interaction. F3, F6, and F9 were optimized based on in vitro floating characteristics, swelling/expanding ability, and unfolding time. All developed formulations were unfolded within 14-22 min after capsule disintegration. The F3 was selected as the final formulation as its ability to control the release of the drug for 24 hrs followed by zero-order kinetics having super case 2 transport. XRD confirmed the amorphousness of the drug within the formulation. The stability study results revealed that the formulation was quite stable at extreme storage conditions. Conclusion: The developed novel formulation has good potential for the effective management and treatment of diabetes mellitus.

Design of a self-unfolding delivery concept for oral administration of macromolecules

Delivering macromolecular drugs, e.g. peptides, to the systemic circulation by oral administration is challenging due to their degradation in the gastrointestinal tract and low transmucosal permeation. In this study, the concept of an oral delivery device utilizing an elastomeric material is presented with the potential of increasing the absorption of peptides, e.g. insulin. Absorption enhancement in the intestine is proposed as a result of self-unfolding of a polydimethylsiloxane foil upon release from enteric coated capsules. A pH-sensitive polymer coating prevents capsule disintegration until arrival in the small intestine where complete unfolding of the elastomeric foil ensures close contact with the intestinal mucosa. Foils with close-packed hexagonal compartments for optimal drug loading are produced by casting against a deep-etched silicon master. Complete unfolding of the foil upon capsule disintegration is verified in vitro and the insulin release profile of the final delivery device confirms insulin protection at gastric pH. In vivo performance is evaluated with the outcome of quantifiable plasma insulin concentrations in all rats receiving duodenal administration of the novel delivery device. By taking advantage of elastomeric material properties for drug delivery, this approach might serve as inspiration for further development of commercially viable biocompatible devices for oral delivery of macromolecules.

An Ingestible Self-Polymerizing System for Targeted Sampling of Gut Microbiota and Biomarkers.

A proof-of-concept for the fabrication of a self-polymerizing system for sampling of gut microbiome in the upper gastrointestinal (GI) tract is presented. An orally ingestible microdevice is loaded with the self-polymerizing reaction mixture to entrap gut microbiota and biomarkers. This polymerization reaction is activated in the aqueous environment, like fluids in the intestinal lumen, and causes site-specific microsampling in the gastrointestinal tract. The sampled microbiota and protein biomarkers can be isolated and analyzed via high-throughput multiomic analyses. The study utilizes a hollow microdevice (Su-8, ca. 250 μm), loaded with an on-board reaction mixture (iron chloride, ascorbic acid, and poly(ethylene glycol) diacrylate monomers) for diacrylate polymerization in the gut of an animal model. An enteric-coated rat capsule was used to orally gavage these microdevices in a rat model, thereby, protecting the microdevices in the stomach (pH 2), but releasing them in the intestine (pH 6.6). Upon capsule disintegration, the microdevices were released in the presence of luminal fluids (in the small intestine region), where iron chloride reacts with ascorbic acid, to initiate poly(ethylene glycol) diacrylate polymerization via a free radical mechanism. Upon retrieval of the microdevices, gut microbiota was found to be entrapped in the polymerized hydrogel matrix, and genomic content was analyzed via 16s rRNA amplicon sequencing. Herein, the results show that the bacterial composition recovered from the microdevices closely resemble the bacterial composition of the gut microenvironment to which the microdevice is exposed. Further, histological assessment showed no signs of local tissue inflammation or toxicity. This study lays a strong foundation for the development of untethered, non-invasive microsampling technologies in the gut and advances our understanding of host-gut microbiome interactions, leading to a better understanding of their commensal behavior and associated GI disease progression in the near future.

In vivo characterization of enTRinsic™ drug delivery technology capsule after intake in fed state: A cross-validation approach using salivary tracer technique in comparison to MRI

The instability of various small molecules, vaccines and peptides in the human stomach is a complex challenge for oral drug delivery. Recently, a novel gastro-resistant capsule – the enTRinsic™ Drug Delivery Technology capsule – has been developed. In this work, the salivary tracer technique based on caffeine has been applied to study the in vivo disintegration of enTRinsic™ capsules in 16 healthy volunteers. In addition, magnetic resonance imaging (MRI) was used to visualize GI transit and to verify the disintegration times determined by using the salivary tracer technique. The enTRinsic™ capsules filled with 50mg of caffeine and 5mg of black iron oxide were administered in the fed state, i.e. 30min after a light meal (500kcal). In the first hour after capsule intake, the subjects were placed in supine position in the MRI scanner and scans were performed in short time intervals. After 1h, the subjects could leave the MRI scanner in between the MRI measurements, which were performed every 15min until disintegration of the capsule was confirmed (maximum observation time: 8h). Saliva samples were obtained simultaneously with MR imaging. Caffeine concentrations in saliva were determined by LC/MS-MS. The starting point of capsule disintegration was determined visually by inspection of the MR images as well as by the onset of salivary caffeine concentrations. In 14 out of 16 subjects, the capsule disintegrated in the small intestine. In one subject, the enTRinsic™ capsule was not emptied from the stomach within the observation time. In another subject, disintegration occurred during gastric emptying in the antropyloric region. In this study, we demonstrated that the enTRinsic™ capsules are also gastro resistant when taken under fed state conditions. Furthermore, we demonstrated the feasibility of using low dose caffeine as a salivary tracer for the determination of the disintegration of an enteric formulation.

Combined Application of MRI and the Salivary Tracer Technique to Determine the in Vivo Disintegration Time of Immediate Release Formulation Administered to Healthy, Fasted Subjects.

The process of disintegration is a crucial step in oral drug delivery with immediate release dosage forms. In this work, the salivary tracer technique was applied as a simple and inexpensive method for the investigation of the in vivo disintegration time of hard gelatin capsules filled with caffeine. The disintegration times observed with the salivary tracer technique were verified by magnetic resonance imaging (MRI). After an overnight fast of at least 10 h and caffeine abstinence of minimum 72 h, conventional hard gelatin capsules containing 50 mg caffeine and 5 mg iron oxide were administered to 8 healthy volunteers. For the period of 1 h after capsule intake, subjects were placed in supine position in the MRI scanner, and scans were performed in short time intervals. Each MRI measurement was directly followed by saliva sampling by drooling. Salivary caffeine concentrations were determined by high performance liquid chromatography followed by mass spectrometric detection (LC/MS-MS). The time point of capsule disintegration was determined by visual inspection of the MR images as well as by an increase in the salivary caffeine concentration. The results indicated that the difference in mean disintegration times of the capsules as determined by the two in vivo methods was around 4 min (8.8 min for MRI vs 12.5 min for saliva). All disintegration times determined by the salivary tracer technique were slightly higher. This delay could be explained by the fact that the appearance of caffeine in saliva required drug absorption in the small intestine. Because capsule disintegration happened mainly in the stomach, the exact site of disintegration as well as the processes of gastric mixing and gastric emptying contributed to the delay between the two methods. This work demonstrated the feasibility of the salivary tracer technique to investigate the in vivo disintegration of immediate release dosage forms in a simple and reliable manner.

Design and Evaluation of a New Fixed-Dose Immediate Release Capsule of Atenolol, Enalapril Maleate and Hydrochlorothiazide

Aim and Objectives: To design, formulate and perform in vitro studies of a fixed dose combination (FDC) immediate release solid dosage form of the antihypertensive drugs atenolol, enalapril and hydrochlorothiazide. The objectives of the study were to perform pre-formulation studies, design an immediate-release FDC capsule dosage form, and evaluate the prepared dosage form. Methods: Differential Scanning Calorimetric (DSC) analysis of physical mixtures of drugs and drug-excipient combinations was used to assess compatibility. Binary mixtures of atenolol and enalapril form a eutectic mixture indicating that a tablet dosage form, in which the drugs would be highly compressed together, may not be stable. Hard gelatin shell encapsulation was therefore employed. Atenolol and enalapril were separately dry-granulated with hydrochlorothiazide and excipients and mixed together at appropriate therapeutic proportions and encapsulated in size 1 hard gelatin capsules (HGC). Preliminary screening produced five formulations each with similar proportions of the 3-drug FDC but with 5 different levels of disintegrant. Capsule weight variation, disintegration time and dissolution rate were determined as output variables, following USP procedures. For the dissolution studies, a reverse phase high-pressure liquid chromatographic (RP-HPLC) method was developed for simultaneous analysis of the three drugs. Results: Granules possessed good fluidity (compressibility index 8.53 to 11.63 and tapped bulk density 1.09 to 1.132). Capsule disintegration time was generally £ 2 minutes while 80% of each drug dissolved within 20 minutes. Capsules showed no sign of physical instability or adverse effect during a period of 1 year shelf storage at room temperature (average temperature 25°C). Conclusions: Granules possess adequate fluidity and compressibility for filling into HGC. Results generally indicated that an immediate release FDC capsule of atenolol, enalapril and hydrochlorothiazide was stable for more than 1 year of observation. Capsule disintegration time and dissolution rate were generally within the USP specification.

Bacterial Enzyme Responsive Polymersomes: A Closer Look at the Degradation Mechanism of PEG-block-PLA Vesicles

Stimuli-responsive polymersomes that are selectively cleaved by enzymes of pathogenic bacteria are herein reported. The local disruption of the polyester wall in poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) polymersomes filled with reporter dyes owing to enzymatic degradation by proteinase K was monitored by fluorescence lifetime imaging microscopy. Capsule opening occurred on timescales of minutes to hours, leading to the release of the dye, followed by a slow capsule disintegration, and finally cleavage into monomeric lactic acid over several weeks. These nanocontainers represent a promising element in novel theranostic systems for potential application in advanced wound dressings.

English

The objectives of the work were to evaluate the binder properties of gum from Irvingia wombolu seed cotyledons and to compare with sodium carboxymethylcellulose (SCMC) in tramadol encapsulated granules. Tramadol granules was formulated by wet granulation using gum derived from the seed cotyledons of I. wombolu as binder at concentrations of 2.5, 5.0, 7.5, 10.0 and 15.0% w/w. The binder properties of the gum were compared with that of SCMC. The flow properties of the granules were studied by direct and indirect methods. The tramadol capsules were evaluated using necessary official tests. The phytochemical and physicochemical properties of the gum were also studied. The results showed that tramadol granules exhibited good flow for the production of quality capsules. Tramadol capsules formulated with Irvingia wombolu gum and SCMC, respectively complied with BP specification for capsules weight uniformity with percentage deviations below 10%. Capsule disintegration time ranged from 4.80 &plusmn; 0.43 min to 5.90 &plusmn; 0.45 min for tramadol capsules formulated with I. wombolu gum and were not significantly affected by concentration of gum in the formulation (p &lt; 0.05). However, tramadol capsules formulated with I. wombolu gum exhibited faster disintegration time than SCMC (p &lt; 0.05) whose disintegration time occurred at 14.20 &plusmn; 0.87 min. The results of phytochemical analysis of I. wombolu gum showed that the gum contains alkaloids, flavonoids, saponin, tannins and glycosides. Therefore, natural gum from I. wombolu has good potential to be used in formulating normal release tramadol capsules. Key words: Irvingia wombolu gum, physicochemical characterization, micromeritic studies, capsule production.

Study of dissolution profiles and desintegration of capsules containing the dried hydroethanolic extract of Calophyllum brasiliense

Calophyllum brasiliense Cambess, Calophyllaceae, is of great interest in folk medicine and is used in the treatment of various diseases such as diabetes. Granules containing the hydroethanolic extract from the stem bark of C. brasiliense were obtained. The polyphenol content was standardized, and the average weight, disintegration, and the dissolution proi les of the capsules were determined after encapsulation. The capsules had an average weight of 574.5±8.0 mg. In vitro tests showed that the most efi cient disintegration proi le was in hydrochloric acid buffer (pH 1.2), with a capsule disintegration time within 9 min. The dissolution analysis showed a better uniformity of capsule content release when the test was performed in a hydrochloric acid buffer (pH 1.2), with a maximal release rate at 15 min (giving a polyphenol content of 4.38%, which corresponds to a concentration of 0.0080 mg/mL). In distilled water, the maximal release was reached at 20 min (giving a polyphenol content of 5.41%, which is equivalent to 0.0105 mg/mL). In phosphate buffer, the maximal release of capsule contents was reached at the end of the dissolution assay (30 min), with the lowest amount of released polyphenols (3.61%, which corresponds to a concentration of 0.0070 mg/mL). The encapsulated form of the hydroethanolic extract of C. brasiliense was shown to have the necessary traits of a desirable delivery agent, and the dissolution test was an effective analysis of this material's polyphenol release proi le for the specii c dosage form.