Hypromellose Capsules Research Articles

СРАВНИТЕЛЬНАЯ ОЦЕНКА ВЛАГОСОРБЦИОННЫХ СВОЙСТВ ЖЕЛАТИНОВЫХ И ГИПРОМЕЛЛОЗНЫХ ТВЕРДЫХ КАПСУЛ

Aim. Comparative evaluation of the shells of solid capsules made of gelatin and hypromelose of hygroscopicity and disintegration indicators. Materials and Methods. Solid gelatin and hypromellose capsules produced by Capsugel (Belgium), as well as pharmaceutical compositions with bifidobacterium lyophilisate were used as objects of research. Hygroscopicity was determined according to FEES methods. Hygroscopicity is determined by the weight method according to the GF RF XV according to the OFS.1.1.0042 "Determination of hygroscopicity". The water-absorbing properties of capsule shells were evaluated by the rate of moisture gain of empty and filled solid capsules. Tests on the disintegration index were conducted according to the GF of the Russian Federation XV, OFS.1.4.2.0013 "Disintegration of solid dosage forms", OFS.1.7.1.0003.15 "Bifido-containing probiotics". Results. Comprehensive pharmaceutical-technological studies of empty hard capsules and model samples with encapsulated composition with bifidobacterium lyophilisate in hard capsules produced by Capsugel® (Belgium) were carried out. As a result of comparative analysis of characteristics of empty hard capsules Coni-Snap and Vcaps Plus, it was revealed that Vcaps Plus capsules have faster disintegration, higher rate of moisture gain, low hygroscopicity of the capsulated composition with preservation of the shape and structure of the capsule shell. Conclusion. Comparative studies of the water-absorption properties of gelatin and hypromellose capsules have shown the rationality of using hypromellose capsules for encapsulating hygroscopic AFS, in particular lyophilizates.

Biodegradable capsules as a sustainable and accessible container for vitrification of gonadal tissue using the zebrafish animal model

Cryopreservation of fish gonadal tissue is an important technique for preserving genetic variability. However, this technique involves the use of cryotubes, plastic containers with low degradability that are expensive and difficult to obtain in certain parts of the world. Therefore, this study aimed to evaluate the efficiency of gelatin and hypromellose hard capsules as a sustainable and accessible alternative container to the cryotube for vitrification of zebrafish (Danio rerio) gonadal tissue. The gonadal tissues (testicular or ovarian) were vitrified in cryotubes, hard-gelatin, and hard-hypromellose capsules. Gelatin capsules exhibited comparable efficacy to cryotubes in preserving spermatogonia viability (33.03 ± 10.03 % and 37.96 ± 8.35 %, respectively), whereas hypromellose capsules showed decreased viability (18.38 ± 2.09 %). Immature oocyte viability remained unaffected by the capsule materials, with no difference compared to cryotubes at all oocyte stages (Primary Growth: p < 0.0001; Cortical Alveolar: p < 0.0001; Vitellogenic: p < 0.0001). Mitochondrial activity and lipid peroxidation demonstrated no difference among cryotubes and capsules for both gonadal tissues. However, antioxidant activity was notably higher in gelatin capsules (Testes: 147.2 ± 32.32 μg; Ovary: 87.98 ± 10.91 μg) than in cryotubes (Testes: 81.04 ± 26.05 μg; Ovary: 54.35 ± 11.23 μg) and hypromellose capsules (Testes: 62.36 ± 17.10 μg; Ovary: 63.96 ± 7.51 μg), likely due to the inherent antioxidant properties of gelatin. The results obtained in this study demonstrate that the cryotube can be replaced by gelatin capsules for vitrification of both gonadal tissues of zebrafish, being a sustainable and accessible alternative as it is a low-cost and environmentally friendly container.

Dry powder formulations of hyperimmune serum.

Effective strategies against the spread of respiratory viruses are needed, as tragically demonstrated during the COVID-19 pandemic. Apart from vaccines, other preventive or protective measures are necessary: one promising strategy involves the nasal delivery of preventive or protective agents, targeting the site of initial infection. Harnessing the immune system's ability to produce specific antibodies, a hyperimmune serum, collected from an individual vaccinated against SARS-CoV-2, was formulated as a dry powder for nasal administration. The selection of adequate excipients and process are key to maintaining protein stability and modulating the aerodynamic properties of the powders for reaching the desired respiratory regions. To this end, a hyperimmune serum was formulated with trehalose and mannitol as bulking agents during spray drying, then the ability of the redissolved immunoglobulins to bind Spike protein was verified by ELISA; foetal bovine serum was formulated in the same conditions as a reference. Moreover, a seroneutralization assay against SARS-CoV-2 pseudoviruses generated from different variants of concern was performed. The neutralizing ability of the serum was slightly reduced with respect to the starting serum when trehalose was used as a bulking agent. The powders were loaded in hypromellose capsules and aerosolized employing a nasal insufflator in an in vitro model of the nasal cavity connected to a Next Generation Impactor. The analysis of the powder distribution confirmed that all powders were inhalable and could target, at the same time, the upper and the lower airways. This is a preliminary proof-of-concept that this approach can constitute an effective strategy to provide broad coverage and protection against SARS-CoV-2, and in general against viruses affecting the airway. According to blood availability from donors, pools of hyperimmune sera could be rapidly formulated and administered, providing a simultaneous and timely neutralization of emerging viral variants.

Technologic Considerations of Creation Dosage Form of Original Substance 3,7-diazabicyclo[3.3.1]nonane

Introduction. An innovative pharmaceutical substance based on the 3,7-diazabicyclo[3.3.1]nonane derivative provides long-term activation of AMPA receptors and the production of neurotrophic factors, which makes it possible to use it for the treatment of cognitive impairments and rehabilitation of patients who have undergone acute brain hypoxia. Given that this substance is able to be absorbed through the walls of the gastrointestinal tract and pass through the blood-brain barrier, there are no restrictions on the development of an oral dosage form. In addition, the oral dosage form has significant advantages when used in geriatric and pediatric practice.Aim. The aim of the work was to carry out a comparative study of the possibility of using gelatin and hypromellose capsules for the development of the composition and technology for obtaining a dosage form containing a pharmaceutical substance based on a 3,7-diazabicyclo[3.3.1]nonane derivative.Materials and methods. The study of the «Dissolution» test of gelatinous and hypromellose capsules was carried out on an ERWEKA DT 720 «Paddle stirrer» apparatus at a stirrer rotation speed of 50 rpm in three media: pH 1.2, pH 4.5 and pH 6.8. The content of the substance in each sample was determined by high performance liquid chromatography with UV detection.Results and discussion. The results of the development and testing of capsules containing an original pharmaceutical substance of nootropic action based on a derivative of 3,7-diazabicyclo[3.3.1]nonane, which has low pharmaceutical and technological characteristics and is practically insoluble in water, are presented. The D/S value was ≥250.00 ml in each physiological pH range. The results of determining the dissolution of the developed dosage form in three media at pH values of 1.2, 4.5 and 6.8 showed a positive effect of the technology used on the solubility of the substance.Conclusion. A significant increase in the solubility of the practically insoluble substance of the 3,7-diazabicyclo[3.3.1]nonane derivative in the developed dosage form was shown, which is the result of the use of a well-founded complex of excipients and the technology of moisture-activated granulation. According to the results obtained, (77.60 ± 2.50) % of the substance passes into the dissolution medium with a pH of 4.5 in 45 minutes. The research results are used to develop a technological scheme for obtaining a finished dosage form, its indicators and quality standards.

DEVELOPMENT OF THE COMPOSITION AND TECHNOLOGY FOR THE PRODUCTION OF ENCAPSULATED DRUGS BASED ON 3,7-DIAZABICYCLO[3.3.1]NONANE

The following biological and pharmaceutical factors influence the therapeutic efficacy and bioequivalence of drugs: physicochemical properties of a pharmaceutical substance, bioavailability, type of dosage form, route of administration, nature of excipients, their compatibility, as well as technological conditions of production, including the preparation of drugs forms. Before mass production of a drug, the technological parameters and characteristics of the pharmaceutical substance must be carefully studied and scientifically substantiated. This work is devoted to the study of the technological properties of an original pharmaceutical substance based on the derivative of 3.7-diazabicyclo[3.3.1]nonane with the chemical name IUPAC 6-[4methoxy-3- (1H-pyrazol-1-ylmethyl) benzyl] -1,11dimethyl-3,6,9-triazatricyclo[7.3.1.1]tetradecane-4,8,12-trion, used as an active substance for the development of the composition and technology for the preparation of oral dosage forms in capsule form. The article presents the results of the development and testing of a drug in the form of capsules of the original pharmaceutical substance of the nootropic action of 3,7-diazabicyclo[3.3.1]nonanane, which is practically insoluble in water. The study identified and evaluated the technological and biological properties of a pharmaceutical substance that can affect the pharmacological activity in the production of a dosage form. The study examined the key indicators: solubility, particle size, flowability, bulk density. The technological characteristics of the pharmaceutical substance are studied not only by certain values of the indicated characteristics but also by the values of the Hausner and Carr indices. The data obtained suggest the content and progress of further stages of pharmaceutical development. The presence of the lag phase when dissolving hypromellose capsules in a medium with a pH of 1,2 and relatively low disintegration rates in media with a pH of 1,2, pH 4,5, and pH 6,8 served as the basis for the choice of gelatin capsules. The developed dosage form meets modern pharmacopoeial requirements, including the dissolution kinetics: according to the results obtained, in 45 minutes (77,6 ± 2,5)% of the substance passes into the dissolution medium with a pH of 4,5. The results of the study are used to develop a technological scheme for obtaining the dosage form of 3,7-diazabicyclo[3.3.1]nonane, its indicators, and quality standards.

A comparative study of hard gelatin and hypromellose capsules containing a dry extract of senna (Cassia angustifolia) under controlled temperature and relative humidity.

Dried natural extracts demand challenges to the production process, especially when encapsulated in hard shells to avoid compromising the integrity of the capsule and extract. The present study describes a preliminary comparative approach on the changes in properties of hard gelatin and hypromellose capsules containing senna (Cassia angustifolia Vahl) leaf dry extract under two storage conditions. Therefore, loss on drying, disintegration, resistance to breakage, water activity, and microbial contamination after 6 mo at 30°/65% RH and 40°/75% RH were evaluated using Pharmacopoeia, AOAC and the manufacturer´s methods. The contents of sennoside A and sennoside B in the capsules were assessed by HPLC. Fine-tosuperfine powder of the extract presenting 0.14% total ash and 2.9% loss on drying was applied. Uniformity of mass was repeatable independently of gelatin and hypromellose shells (p > 0.05, t-test). The hypromellose capsules were more resistant to breakage than those of gelatin (maxima broken of 1/100 versus 42/100), in which the water content (2.9% to 5.7%) and water activity (0.33 to 0.43 aw) of the extract were intensively increased and, additionally, an acceptable increase in microbial contamination was observed. Compared to hypromellose shells, gelatin capsules did not maintain the same levels of both sennosides at 40°/75% RH, while sennoside B was lower. In conclusion, hypromellose performed better than gelatin to provide stable capsules, for resistance to breakage and disintegration unchanged, and offered higher protection to senna dry extract against humidity, microbial contamination and sennoside degradation. Overall, these preliminary results suggest the use of hypromellose encapsulation as a good alternative to gelatin in the production of medicinal capsules containing herbal dry extracts, mainly those with high hygroscopicity, and provide preliminary support for designing stability studies of capsules containing dry extracts that present high hygroscopicity.

Impact of capsule type on aerodynamic performance of inhalation products: A case study using a formoterol-lactose binary or ternary blend

The aerodynamic performance of a dry powder for inhalation depends on the formulation and the dry powder inhaler (DPI). In the case of capsule-based DPIs, the capsule also plays a role in the powder aerosolisation and the dispersion of the micronized drug during the inhalation. This study evaluated the impact of gelatine capsules (Quali-G™ and Hard Gelatine Capsules for DPIs), cold-gelled hypromellose (HPMC) capsules (Quali-V®-I and Vcaps®) and thermal-gelled HPMC capsules (Vcaps®Plus) from Qualicaps® and Capsugel® respectively, on the delivered dose (DD), fine particle dose (FPD), and capsule retention for formoterol-lactose binary and ternary blends. This study used a low resistance Axahaler® DPI based on the RS01 design (Plastiape, Italy). Similar trends were observed with the different capsule types that packaged both dry powder formulations. The highest DD and FPD and the lowest formoterol capsule retention were observed with cold-gelled HPMC capsules such as Quali-V-I® and Vcaps®, without significant differences between these capsules (p > 0.05, one-way ANOVA with Newman-Keuls post-hoc test) for both dry powders. Therefore, the capsule composition and manufacturing process have an influence on aerodynamic performance. In addition, the ternary blend showed higher DDs and FPDs but also higher capsule retention in comparison to the binary blend.

Simple Strategy to Protect Lactase Activity in Solid Formulation.

Lactose intolerance is characterized by the absence of the enzyme lactase (beta-galactosidase) and affects two thirds of the world adult population. Our aim was to evaluate a lactase gastro-resistant formulation to ensure increased activity in the action site of the enzyme (lumen of the small intestine). Simultaneously, we also evaluated the commercial product stability and enzyme activity, because the product containing beta-galactosidase is classified as food supplement according to the Food and Drug Administration (FDA), so it is free to pass quality testing, efficacy and stability. So, it is possible that contain some irregularities as to the content and enzymatic activity. The dissolution assay was performed using a dissolution test system and commercial product and the gastro-resistant formulation were evaluated according to a method adapted to the conditions recommended by United States Pharmacopeia (US Pharmacopeia) for gastro-resistant formulations. For the assessment of enzymatic activity throughout the dissolution test was employed the official method of lactase assay described in US Pharmacopoeia. This method is based on a colorimetric reaction which the substrate reacts with the enzyme generate a colored product further analyzed by UVVisible spectrophotometry. When carrying out dissolution test in commercial product it is noted that the existing formulation is not able to protect the enzyme from degrading action of gastric environment (a loss of 86.0 ± 0.8% of lactase activity was observed). Our proposed gastro-resistant pharmaceutical form there was no loss of activity during the acid step and the end of the dissolution test the found activity was 95 ± 1.3%. The formulations proposed in this work using hypromellose capsules ensure the enzymatic activity of lactase, preventing its contact with the acid medium. For the other side, the results of commercial tablets for lactase release indicate a significant loss of enzyme activity due to the immediate release of the enzyme in the simulated gastric fluids.

Survival of Probiotics in Hypromellose Capsules with Rice or Potato Maltodextrin Excipient.

There is currently no authorized or established therapeutic level/dose of probiotics for proposed health benefits; however, a daily probiotic consumption of 108 to 1010 CFU has been recommended. This study determined the survival of 5 individual probiotic strains, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium lactis, along with a mixture of the 5 strains in hypromellose capsules with rice or potato maltodextrin at 4, 25, and 37 °C for 12 mo. Samples were collected monthly and plated on deMan-Rogosa Sharpe agar with 0.05% l-cysteine hydrochloride. Results showed that samples stored at 4 °C had an average count of 108 to 1011 CFU/g of probiotic cells during the 12 mo period, whereas at 25 °C, L. rhamnosus and L. paracasei had an average counts below 108 CFU/g during the storage period. L. rhamnosus was the most vulnerable strain used in this study, having the least viable counts at all 3 storage temperatures. Probiotics stored in rice maltodextrin, on average, had higher probiotic counts compared to those stored in potato maltodextrin. Study suggests that to provide consumers with 108 to 1010 CFU/d of probiotic cells, robust bacterial strains, suitable carriers, and a storage temperature of 4 °C are required.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Bolus matrix for administration of dietary markers in horses

External markers are useful or required to estimate forage intake, digestibility, faecal output and passage rate in horses. Oral administration is challenging because of horses’ high sensitivity and selection skills. A suitable bolus matrix should ensure high and consistent acceptance. Boluses were investigated with and without labelling. Synthetic alkane wax, embedded in filter paper or contained in hypromellose capsules, was used as a test marker. Boluses were baked (100°C, 30min) or freeze-dried. The freeze-dried boluses varied in size (1.5, 2, or 3cm Ø) and drying time (6, 12, 24, or 48h). In two tests (AT1 and AT2), acceptance by the horses was assessed with scores between 1 (complete intake) and 4 (refusal). In AT1, marginal rejection of the marker was recorded, whereas the following tests were performed with placebos only. In two bending tests (BT1 and BT2), the force required to break the boluses (FL, flexural load) was determined because this may affect acceptance. Pre-selected variants were stored for 4 weeks in closed boxes under controlled conditions (20°C and light for 16h/d, 16°C and night for 8h/d, and 65% relative humidity) and were subsequently analysed for residual moisture (RM) and spoilage-indicating microbes. In baked boluses, the alkanes were partly found outside of the inner matrices. This was not evident in the freeze-dried variants. Acceptance of the labelled boluses (scores≤1.7±0.18, AT1), baked placebos (scores≤2.2±0.35, AT1) and the freeze-dried placebos (scores≤1.1±0.31, AT2) was consistently high. This was explained by the BT, with a mean FL of 202±16.5N for the baked (BT1) and up to 257±22.5N for the freeze-dried placebos (BT2) being obtained, which was close to the masticatory forces in horses. However, when the boluses distinctly exceeded a size of 3cm Ø, this size probably led to increased FL (BT1), thereby depressing the acceptance of the dried placebos (AT1). The results indicated that the adaption to suitable boluses can lead to increased acceptance. Limiting the drying time to at most 24h seemed justified, especially for the smaller boluses. After 6 and 12h, the RM was 7.5±0.52% (1.5cm Ø) and 5.7±0.52% (2cm Ø), which make the risk of microbial spoilage appear low. Tested boluses were unspoiled for up to 1 month after preparation. It was suggested that the variable sizes of the boluses may enable the use of various marker dosages and, incidentally, also use in different target animals. A freeze-dried matrix is likewise open to use with other thermolabile markers or substances. We recommend the pre-administration of placebos prior to marker administration to ensure high acceptance of the labelled boluses.

Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81μg/capsule=60mg/kg MO), medium (15.97μg/capsule=90mg/kg MO) and high (23.23μg/capsule=127mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60mg/kg MO. Furthermore, the 90 and 127mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena.

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules

The purpose of this study was to assess the in vitro performances of “vegetable” capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

The development of a sensitive methodology to characterise hard shell capsule puncture by dry powder inhaler pins

In order for hard-shell capsules to function effectively as drug reservoirs in dry powder inhalers, the capsule must be punctured with sharpened pins to release the powdered medicament upon inspiration. Capsule performance in this setting is poorly understood. This study aims to develop a methodology to characterise hard shell capsule penetration by needles from commercial dry powder inhalers, to determine whether changes to capsule materials impact on their performance. Two pin types from two commercial dry powder inhalers were mounted in a material-testing machine, equipped with a 500 N load cell. A stainless steel bush was used to secure a capsule directly below the steel pin. Hypromellose (n=10) and gelatin capsules (n=10) were conditioned in 'normal' or low humidity conditions and were subsequently punctured with both types of pin. Each puncture event was recorded on a load-displacement curve. The force required for puncture was 2.82±0.26 N for hypromellose capsules and 4.54±0.26 N for gelatin capsules, stored in normal humidity. Different capsule materials possessed distinguishable signature profiles but repeated force-displacement profiles were highly reproducible i.e. intra-individual variability was minimal. A rapid, robust yet sensitive methodology has therefore been developed that is able to characterise hard shell capsule materials based on the puncture performance.

Corrigendum to: On the performance qualification of hypromellose capsules

Corrigendum to: On the performance qualification of hypromellose capsules

Performance qualification of a new hypromellose capsule: Part II. Disintegration and dissolution comparison between two types of hypromellose capsules

This Part II paper describes the disintegration and dissolution aspects of the qualification of a new hypromellose capsule (HPMC Shell 2). This new capsule does not contain any gelling agent, and is manufactured by a thermal gelation process. Rupture time of the carrageenan-containing capsule (HPMC Shell 1) and HPMC Shell 2, as measured by an improved real-time detection method, showed only slight differences that did not manifest in vivo. The absence of a gelling agent appeared to give HPMC Shell 2 advantages in dissolution in acidic media and in buffers containing potassium ions. Slow drug release of HPMC Shell 1 in 0.1 M HCl was attributed to the interaction of carrageenan with drug compounds; whereas the presence of potassium ions, a gelling promoter for carrageenan, caused delay in capsule opening and larger capsule-to-capsule variation. Disintegration and dissolution performances of both hypromellose capsules are comparable in other dissolution media tested. Based on the superior dissolution performances and quality attributes in terms of physical, mechanical and processability that were detailed in Paper I, the new hypromellose capsule was satisfactorily qualified and has since been used in nearly 20 investigational new drug (IND) compounds.

A Comparison of the Puncturing Properties of Gelatin and Hypromellose Capsules for Use in Dry Powder Inhalers

This study investigates capsule puncture in dry powder inhalers. Gelatin and hydroxypropylmethyl cellulose (HPMC) capsules (stored at 11 and 33% relative humidities) were punctured using a pin from a Foradil® inhaler, with insertion force measurement via an Instron tester. In HPMC capsules, the force after capsule puncture reduced by half and then increased to a second maximum as the pin shaft entered the hole. In gelatin capsules, the postpuncture force reduced to zero, indicating shell flaps losing contact with the pin. At lower moisture contents, both capsules were less flexible. This provides a tool to measure the shell properties of inhalation capsules.

Hard Gelatin and Hypromellose (HPMC) Capsules: Estimation of Rupture Time by Real-time Dissolution Spectroscopy

ABSTRACTThe objective of this study was to measure rupture time of gelatin and hypromellose (hydroxypropyl methylcellulose or HPMC) capsules using a novel approach based on real-time dissolution spectroscopy. Rupture time was measured in standard dissolution apparatus at a constant temperature using a dip-type fiber-optic probe. Labrasol released from the capsules was treated as the marker of the rupture process. Light scatter generated by the emulsified labrasol was detected by an ultrafast monochromator at scan rates approximating 24,000 nm/min. This technique was validated by measuring the dissolution time of gelatin capsules. Rupture times of hypromellose capsules were studied as a function of capsule size, capsule grade, and dissolution medium. Statistical correlations were analyzed by ANOVA. Rupture time of hypromellose capsules was dependent on both the medium and the grade of the capsule, and was independent of capsule size. The composition of the dissolution medium contributes to the rupture time of the capsules and should be considered when fast release and quick biological response is desired. Release delay, however, may not manifest itself in vivo and the time to maximum plasma concentration may not be significant.

A scintigraphic investigation of the disintegration behaviour of capsules in fasting subjects: A comparison of hypromellose capsules containing carrageenan as a gelling agent and standard gelatin capsules

Two-piece hard shell capsules made from hypromellose (or hydroxypropyl methylcellulose, HPMC) have been proposed as an alternative to conventional gelatin capsules for oral drug delivery; however, little is known about their in vivo behaviour. The aim of this study was to compare the disintegration of HPMC and gelatin capsules in fasted human subjects using the technique of gamma scintigraphy. HPMC capsules containing carrageenan as a gelling agent (QUALI-V®, Qualicaps) and gelatin capsules (Qualicaps) of size 0 were filled with a lactose-based mixture. The capsules were separately radiolabelled with indium-111 and technetium-99m. Both capsules were administered simultaneously with 180 ml water to eight healthy male subjects following an overnight fast. Each volunteer was positioned in front of the gamma camera and sequential 60 s images were acquired in a continuous manner for 30 min. No differences in the oesophageal transit of the two types of capsules were noted, with the capsules arriving in the stomach in a matter of seconds. All the capsules disintegrated in the stomach. The mean (±S.D.) disintegration time for the HPMC capsules was 9 ± 2 min (range 6–11 min). The corresponding mean time for the gelatin capsules was 7 ± 4 min (range 3–13 min). These disintegration times were not significantly different ( P = 0.108, paired t-test). In conclusion, HPMC and gelatin capsules show rapid and comparable in vivo disintegration times in the fasted state. HPMC capsules containing carrageenan as a gelling agent therefore offer a practical alternative to gelatin capsules as an oral drug delivery carrier.

Evaluation and Comparison of Physicomechanical Characteristics of Gelatin and Hypromellose Capsules

ABSTRACTThe aim of this study is evaluation and comparison of physical and mechanical properties of hypromellose and gelatin capsules. For this purpose, the empty and filled capsules of hypromellose and gelatin (size 4) were examined in regard with their physical and mechanical characteristics, employing textural analysis, and disintegration properties in various immersion fluids, utilizing a USP 28 disintegration apparatus. The results demonstrated that owing to their greater water permeability, gelatin capsules disintegrate much faster than hypromellose shells in all tested media. However, hypromellose capsules showed a more uniform pattern of dispersion in the disintegration fluids. As for mechanical properties, at ambient conditions, gelatin capsules appeared to be harder and stronger with less elasticity as compared with hypromellose shells. On the contrary, at an elevated temperature, gelatin capsules demonstrated lower resilience. This study shows that hypromellose capsules have excellent properties and are promising as far as regulatory, manufacturing, religious, and dietary issues are concerned.