Hard Capsule Shells Research Articles

Characteristics of carrageenan from seaweed hydrolysis using marine fungi as hard-shell capsule material

Carrageenan is a polysaccharide extracted from red algae and can be used as a raw material for hard-shell capsules. Carrageenan can be produced by biological hydrolysis of marine fungi. The viscosity of carrageenan resulting from hydrolysis using marine fungi is lower than that of commercial carrageenan. Gelatine can be used to modify the characteristics of polysaccharide-based materials. The characteristics and types of carrageenan and plasticizers influence the interactions between carrageenan and gelatin. This study aimed to determine the characteristics of carrageenan produced by seaweed hydrolysis of a hard-shell capsule material. The physical characteristics of the carrageenan produced by hydrolysis were determined, including yield, viscosity, and gel strength. The properties of the hard-shell capsules, including dimensions, capsule weight, disintegration time, and moisture content, were analyzed. The yield was 25%, and the viscosity and gel strength of carrageenan were 45 cP and 175 gf, respectively. Carrageenan contains 13% moisture, 8% ash, and 8% cellulose. Semi-refined carrageenan produced by this treatment was used to prepare hard-shell capsules. The capsule made from semi-refined carrageenan had a body length of 18 mm, capsule length of 10 mm, capsule weight of 0.9 grams, disintegration time of 10 min, and moisture content of 12%.

Self-nano-emulsifying Drug Delivery Systems of Atorvastatin Calcium Liquid Filled in Hard Shell Capsules for Improved Oral Bioavailability in Rabbits

Aims and Objectives: Atorvastatin calcium (ATR) is a BCS class II drug showing poor bioavailability due to limited aqueous solubility. In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed and formulated as a liquid filled in a hard shell capsule to improve the bioavailability of ATR. Methods: Different oils were screened through the saturated stability method, and the amount of ATR solubilized in the respective oils was analysed through HPLC at 245nm. A ternary phase diagram was plotted to obtain the optimized ratio of oil, surfactant, and co-surfactant to formulate SNEDDS. The prepared ATR SNEDDS was filled into hard shell capsules, band sealed, and subjected to various evaluations like disintegration time, self-emulsification time, precipitation time assessment, globule size analysis and zeta potential. Then the in vitro dissolution studies were carried out. The optimized SNEDDS formulation was filled in a hard shell capsule, and in vivo studies were performed on rabbits to compare the pharmacokinetic parameters with the marketed formulation and pure ATR. Results: Capmul MCM as the oil component showed five-fold solubility of ATR and was selected for the preparation of ATR-SNEDDS. The SNEDDS formulation showed an entrapment efficiency of 89.76±4.1% ATR with a globule size of 385±1.9 nm and an emulsification time of 5 seconds. It was established from the study that liquid ATR-SNEDDS had relative bioavailability enhanced by 1.7 times in comparison to the marketed formulations (Lipvas) and 4.8 times with respect to pure ATR. Conclusion: From the study, it was concluded that the bioavailability of ATR was enhanced by formulating ATR as Liquid SNEDDS filled in hard shell capsules.

Towards a novel pullulan and pullulan-enteric hard capsules: Study of drug release and crucial capsule features

Pullulan, a natural polymer, is often used as a plant-based alternative polymer for gelatin to produce hard capsules. To the best of our knowledge, there have been negligible studies on the performance of enteric pullulan capsules. Hence, this paper describes a new formulation for enteric pullulan hard capsules that can resist the acidic environment of the stomach and release the drug in the small intestine without the need for an exterior coating. This formulation consists of three polymers, including pullulan, Eudragit L100, and κ-carrageenan, which are used to develop resistance against acid and facilitate gelation to form capsules. With regards to the humidity assessment of target hard capsules, it is estimated that the prepared capsules possess an appropriate potential for target utilizations. The capsules were tested using esomeprazole as a model drug for dissolution testing. The results demonstrated that the enteric hard-shell capsules remained stable for 2 h in 0.1 N HCl at a pH of 1.2 and then ruptured upon entering a phosphate buffer (simulated small intestine) medium at a pH of 6.8. The FESEM and cross-sectional analysis revealed that no drug was released due to the absence of pores on the surface. Rheological examinations also revealed that the prepared solution have a desirable property. It is certified that the NMR spectrum proposes the existence of crosslinking and polymerization of pullulan which signifies appropriate existing interactions polymeric binders and gelling agent. TGA and DSC evaluations are in well accordance with the strong cross-linked structure generated by comprising pullulan polymer with the Eudragit pH-sensitive Polymer. Overall. this new formulation has potential feature for utilization in drug delivery systems where controlled release is desired, especially for drugs that are sensitive to acidic environments in the stomach.

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.

The Rapid Detection of Pork Gelatin in Hard Shell Capsule on Supplement Products Using FTIR and PCA

This study aimed to develop a fast and low-cost detection method to determine the difference between hard shell capsule on supplement products containing pork or non-pork gelatin by using Fourier Transform Infrared (FTIR) spectroscopy and Partial Component Analysis (PCA). Twelve samples of hardshell capsules were used, among which Eight samples were pure made from pork and some of them adulterated with cow. The samples were detected before using real-time PCR to determine the identity of the samples. All the gelatin samples were measured with the FTIR spectrophotometer in the reflection mode. Spectra were collected in the wavenumber range from 4000-650 cm-1. The results show that the PCA model with the data were pre-processed before PCA was performed. The absorbance data from FTIR were pre-processed using Savitsky-Golay smoothing technique and continued with normalization by peak normalize before subjected to PCA. This newly developed method is fast, involves simple sample preparation and is low cost.

Pembuatan Cangkang Kapsul Keras dari Glukomanan Biji Salak (Salacca zalacca) dengan Penambahan Enzim α-Amilase Buah Kelor

The purpose of this study was to examine the results of the fabrication and disintegration time of hard capsule shells made from salak seed glucomannan with and without the inclusion of α-amylase moringa fruit enzymes. To determine the effect of time, temperature, and the optimal concentration on the production of rigid capsule shells from glucomannan from zalacca seeds. This study makes use of both independent and dependent variables. The data was examined using functional group analysis using an FTIR spectrophotometer, and the hemicellulose from the seeds of the salak fruit was converted to glucomannan with the addition of the moringa α-amylase enzyme. The viscosity of the glucomannan gel variations of zalacca seeds differed, with gels from glucomannan flour with concentrations of 8%, 9%, and 10% (w/v) having viscosity values of 32.5 cP, 2049.75 cP, and 8007, 89 cP, respectively. While glucomannan with the Moringa fruit α-amylase enzyme The viscosity value gradually lowered with the addition of Moringa fruit extract. It reduced at 300°C temperature variation of 11221.02 cP, 400°C temperature variation of 11097.14 cP, and 500°C temperature variation of 10754.37 cP. The viscosity value gradually decreased after the addition of the αamylase moringa fruit enzyme. The 10 minute mixing time variation yielded the greatest viscosity value, 10261.74 cP, while the 50 minute mixing time variation yielded the lowest, 8681.76 cP. Furthermore, physical specifications with the inclusion of the α-amylase enzyme in Moringa fruit produced capsule shells that were thinner in color and conformed to conventional capsule shells.

Present tendencies in hard capsule shell technology

Present tendencies in hard capsule shell technology

Preparation, characterization, and in vitro release of microencapsulated essential oil hydroxyapatite pellets filled into multifunctional capsules

Oregano essential oil (EO)–loaded pellets were prepared using calcium phosphate substrates of different specific surface areas (Sw) and as binders EO in water emulsions with low or high EO content, stabilized with polysaccharides (PSC) or a combination of PSC-Eudragit® L100-55 (PSC-PLM) encapsulants. Tri-cafos® 250 with high Sw gave higher EO loading and more spherical pellets with narrow size distribution. These were filled into the following hard-shell capsules: gelatin, hydroxypropyl-methyl cellulose (HPMC) based immediate release (Vcaps® plus), gastro-resistant (DRcaps®) and enteric release (Vcaps® enteric), and pullulan (Plantcaps®). FTIR and Raman spectroscopy showed H-bonding between PSC and EO and between PSC and PLM. Pellet mechanical strength decreased with EO content and pellets made with PSC emulsions were stronger than PSC-PLM pellets proving PSC binder ability. Disintegration and release of EO from capsules filled with immediate release pellets (PSC) or enteric pellets (PSC-PLM) were tested sequentially in pH 1.2 and 6.8. Capsule shell influenced disintegration and release. The release of EO from the PSC pellets within 1 h, at pH 1.2 was from gelatin 82%/85% (for low/high EO emulsions) but from Vcaps® plus and Plantcaps® it was lower, 36%/38% and 45%/70% respectively. DRcaps® and Vcaps® enteric capsules confirmed gastro-resistance. The release of enteric (PCS-PLM) pellets was: from gelatin and Vcaps® plus capsules 21%/23% and 20%/21% respectively, but from Plantcaps® 61%/62%, indicating deactivation of Eudragit® L100-55 functionality in the last case. In all cases, release was complete after 180 min, but release of enteric pellets from Vcaps® plus was slower than from gelatin capsules due to the presence of HPMC.

DEM analysis of powder deaggregation and discharge from the capsule of a carrier-based Dry Powder Inhaler

In carrier-based Dry Powder Inhalers (DPI), fine API powder covers the surface of bigger carrier particles giving rise to dry coated particles, such that their flow properties are improved. In the hard-shell capsule of Cyclohaler DPI, powder deaggregation and discharge occurs as a result of the centrifugal motion and the subsequent aerodispersion to the mouthpiece induced by the patient’s inhalation. In this work, the crucial initial transient of this dispersion process was analysed through DEM (Discrete Element Method) simulations, by considering the solid phase only. The accelerated rotational motion of the capsule was simulated in the frame of reference of an observer rotating with the capsule, appropriately considering fictitious forces. The effect of the vibrations due to collisions between the capsule and the inhaler on powder discharge was evaluated as well for carrier particle systems. The results provide a punctual mapping of the particle-wall collisions within the capsule, allowing the path of the solids to be tracked until discharge. Simulations were carried out on drug-carrier blends with extreme size difference, considering adhesive interactions, elucidating the early-stage dynamics of the detachment process that occurs inside the capsule due to the interactions between particles and between particles and walls.

SYNTHESIS OF NATURAL GELATIN-BASED HARD CAPSULE SHELL FROM CASSAVA STARCH AND HIBISCUS LEAVES GEL

The aim of this work was to prepare gelatin-based hard capsule shells from natural sources, cassava starch and hibiscus leaves. The effects of composition between cassava starch and hibiscus leaves, and temperature on capsule characteristic was investigated. Extraction and gelatinization were the main method which used in this study. A different compositions of cassava starch and hibiscus leaves gel was added into boiling flask for gelatinization for 2 h. Temperature was maintained at 50, 70 and 100 oC. The optimum resultwas obtained at ratio 8:1 of cassava starch and hibiscus leaves gel with 100 oC operation temperature which has specification 7.60% of ash content, 11.24% of moisture, and 15 min dissolution time.According to the result, this study is expected to be used as a reference for the development of natural gelatin-based hard capsule shell synthesis.

Evaluation and Characterization of Hard-Shell Capsules Formulated by Using Goatskin Gelatin.

Gelatin is used as an additive in medicine, food, and cosmetics. Gelatin from goatskin is a new excipient that has not been explored by researchers, including for hard-shell capsules. The aim of this study was to evaluate and characterize the hard-shell capsules produced from goatskin gelatin. The goatskin gelatin was extracted by an acid hydrolysis method, and the functional properties were investigated. Hard-shell capsules were then produced from goatskin gelatin, evaluated, and characterized. The gelatin extracted from goatskin had 56.9% ± 0.95 clarity and a pH of 5.11 ± 0.09, 97.51% ± 1.1 protein content, 9.23% ± 0.08 water content, 0.18% ± 0.07 ash content, 2.08% ± 0.35 fat content, gel strength of 298 ± 2.64 gbloom, and viscosity of 27.33 ± 2.07 mPs. The gelatin has met the requirements to be made into hard-shell capsules. The average weight of the hard-shell capsules produced was 96.9 mg with 8.69 standard deviation. The average size of the body and cap length was 18.84 ± 0.64 mm and 10.98 ± 0.30 mm, respectively. The results of capsule evaluation and characterization were as follows: the pH was 4.82 ± 1,27, water content was 10.03 ± 0.21, disintegration time was 4.02 ± 2.09 min, and there was no microbial growth. Thus, the capsules made have met the requirements and can be produced in a large quantity.

Modulation of Obesity in Sub-Saharan Africa Using Coenzyme Q10

Obesity is a metabolic disease caused by a large buildup of fat in the body and a deficit in energy consumption compared to energy disposal. It has been related to a shorter life expectancy, has been connected to various cancer types, and has been linked to secondary metabolic illnesses such as diabetes, atherosclerosis, and hypertension. Due to an increase in white adipose tissue deposition, oxidative stress can lead to obesity, and obesity can lead to increased oxidative stress in the body. Coenzyme Q10 (Ubiquinone) is an endogenous anti-oxidant with anti-oxidant properties that aids to reduce oxidative stress. It boosts the anti-oxidant activity of superoxide dismutase and glutathione peroxidase, reduces lipid peroxidation, neutralises free radicals, and promotes vitamin E and C regeneration in the body. It can be found in the form of ubiquinol or ubiquinone. CoQ10 may be found in both diet and supplements. It can be made as a syrup, tablet, soft gel capsule, hard shell capsule, or oral powder as a supplement. It is classified as a biopharmaceutical class II compound with low solubility but good permeability. When CoQ10 supplement is taken with a fatty meal, its bioavailability is increased. CoQ10 slows the evolution of obesity-related atherosclerosis and helps to mitigate the harmful bodily environment caused by obesity.

Liquid Filled Hard Shell Capsules: Current Drug Delivery Influencing Pharmaceutical Technology.

Gastric absorption is an upfront route for drug delivery as it is convenient, economical and most suitable for getting the desired systemic effects. Unfortunately, many traditional and newer generation drugs suffer from poor solubility and have lower bioavailability. With a perspective of bringing a novel delivery system in such a condition for old/existing/new drugs, liquidfilled hard capsules hold promise as the delivery system. Anorganizedstate of the art literature review including patents was conducted to accommodate information on the innovations in technology, processes, and applications in the field of liquid filling in hard-shell capsules. The review findings revealed the importance of understanding the impact of liquid filled hard shell capsules would have in use of complex drug molecules, especially the ones sensitive to light and moisture. This technology can have diverse functions to be used for both immediate and delayed drug release. According to the technology point of view, the band sealing in such hardshell capsules helps in protecting against the tampering of capsule fill. The review provides an insight into the progression in the technology forefront related to formulation development of liquid formulations to be filled in hard shell capsules for better therapeutic potentials and convenience to the patients.

Fabrication of delayed release hard capsule shells from zein/methacrylic acid copolymer blends

Hard capsule shells with an inherent delayed release action are useful for oral administration of active ingredients, which are acid-labile and/or enzymatically degradable in the gastric environment, without the need of film coating. The objective of this study was to fabricate delayed release hard capsule shells by the dip coating method. The film coating formulations comprised blends of zein and methacrylic acid copolymer (Eudragit® L100–55), with and without the addition of the plasticizer, polyethylene glycol 1000. The rheology parameters (loss modulus (G'), storage modulus (G") and loss tangent (tan δ, G"/G')) of the film coating solution were measured to investigate the processability. Central composite design was used to investigate the main, interaction and quadratic effects of the proportion of methacrylic acid copolymer, solid content of the film formers and level of polyethylene glycol 1000 on the capsule wall thickness and mechanical strength. Multiple response optimization was further conducted, and the design space was established. The in vitro drug release in simulated gastric and intestinal fluids of three different formulations in the design space was compared. The results showed that the tan δ value after the gelation point should be < 0.9 in order to form a thin and sturdy capsule shell. The gelation time and viscosity of the coating solution were related to the thickness of the capsule shell. The study showed that drug release from the capsule with a specified thickness and mechanical strength can be modulated by varying the ratio of zein to methacrylic acid copolymer. The delayed drug release profile was achieved through the capsule shell fabricated from zein to methacrylic acid copolymer at the ratios of 75:25 and 83.2:16.8, with 10% polyethylene glycol 1000.

Effect of Added Pectin and Microcrystalline Cellulose (MCC) on Capsule Shell Quality

The objective of this study was analyzing the effect of the added pectin and microcrystalline cellulose (mcc) on the capsule shell quality. The method used in this study was by combining the pectin and microcrystalline cellulose composition on capsule shell manufacture. The formulation used to test the capsule shells was through 1 gram, 2 gram, 3 gram of pectin; 0 gram and 1.5 gram of microcrystalline cellulose; 1 gram of glycerol; and, 1 gram of carrageenan. The experiment tests used in this study were through the organoleptic test, the capsule weight test, the moisture test, the pH test, the dissolution time test, and the capsule-length test. The result of this study showed that the recommended formulation used to manufacture the hard capsule shells was through 3 gram pectin and 1.5 gram microcrystalline cellulose. The required temperature to heat the pectin and microcrystalline cellulose was at 90oC with 2.5-hour heating time. The characteristics of the manufactured capsule shells were that it had a turbid colour and irregular shape, the surface was not smooth and the disintegration time was 9 minutes and 21 seconds.&#x0D; &#x0D; Keywords: Capsule Shell, Microcrystalline Cellulose, Pectin, Variation, Testing

Pangasius Fish Skin and Swim Bladder as Gelatin Sources for Hard Capsule Material.

In this paper, we report the extraction and characterization of gelatin from the abundant industrial fishery waste of Pangasius skin and swim bladder and its application as the base material for hard capsule shells. The yield of gelatin ranged between 19 and 23%, content of moisture is 7.6–9.2%, ash is 1.1–1.7%, pH is 4.1–5.2, gel strength is 238–278 bloom, and viscosity is 65–74.7% mP. SDS-PAGE showed all gelatins have chains of α1, α2, and β-peptides. The skin, swim bladder, and mixed gelatins were successfully used in the production of hard capsule shells. The dimensions, weight, disintegration time, and water content properties of the hard capsules from these Pangasius wastes were akin to the standards of commercial capsules.

Influence of the quality of capsule shell on the non-invasive monitoring of medicines using Terizidone as an example

The aim of this study is to investigate the influence of hard capsule shells on the possibility of non-invasive monitoring and authentication of medicines presented in capsules dosage form. It is shown that the NIR measurements followed by the chemometric analysis, reflects all macro-components of the analyzed samples, which are the PVC blister, the capsule shell, and the capsule contents. The special variable selection procedure, based on the pure spectra of all components, makes it possible to develop a model that is insensitive to small variations of the capsule shell. The shrinkage of spectral region can greatly affect the results of the classification.Consequently, in case we are interested in the whole remedy, capsules with deviations in shell properties should be rejected as the substandard ones. If we are only interested in the quality of capsules’ content, the developed model is effective and applicable in the routine testing. The final model helps to understand and demonstrate the reason for the rejection of substandard samples authentication. It also gives a practical signal to the manufacturer to pay attention to the quality of the capsule shells.

Synthesis and characterization of osmotic pump capsules containing polyoxyethylene and pH modifier to control the release of nifedipine

The aim of this study was to formulate osmotic pump capsules (OPCs) to control the release of nifedipine (NP). NP solid dispersion was prepared by solvent evaporation method. The prepared mixture of NP solid dispersion and various excipients were filled into the commercial HPMC hard capsule shells and then coated with cellulose acetate (CA) solution to form NP-OPC. The CA coating solution consisted of CA as semi-permeable membrane, and Poloxamer 188 as pore formers. The impact of addition agents, citric acid and pore formers on in vitro drug release were investigated. Furthermore, the study has highlighted the impact of paddle speed and the pH value of release media, on the release and compared the release with the commercial controlled release tablets. The in vitro drug release study indicated that drug release could reach 95% in 24 h with optimal formulation, and interestingly model fitting showed that the drug release behavior was closely followed to zero-order release kinetics. The pharmacokinetic studies were performed in rabbits with commercial controlled release tablets as reference, both preparations showed a sustained release effect. Compared with traditional preparation methods of OPCs, the new preparation process was simplified without the operation of laser drilling and the sealing process of capsule body and cap, which improved the feasibility of industrial production.

Synthesis and characterization of capsule shells non gelatin grass jelly leaves-seaweed as drug delivery system material

Drug delivery system is a system that describes the journey of a drug to its target location. The main component of the drug delivery system is gelatin. The leaves of grass jelly-seaweed are needed as a raw material for gelatin. The main component of gelling agents in grass jelly leaves and seaweed is a low-methoxy pectin polysaccharide. Pectin from previous study is used as a synthesis material for hard capsule shells with the addition of other ingredients, which are Na-CMC, sorbitol, and water. The characterization results of capsule shells with variations in the composition of grass jelly-seaweed leaves 0: 4, 1: 3, 2: 2, 3: 1, and 4: 0 (A, B, C, D and E) have a disolving time of 12 minutes 45 seconds; 15 minutes 53 seconds; 23 minutes 10 seconds; 15 minutes 35 seconds and 18 minutes 12 seconds. The swelling degree test each of 200%; 266,7%; 303.3%; 586.7% and 643.3%. Furthermore, the shells of grass jelly-seaweed leaf capsules were tested for their material performance in the cefadroxyl disolving test with variations in sampling time of 10, 20, and 30 minutes. Keywords: Cefadroxyl, Drug delivery system, Green grass jelly leaves, Non-gelatin capsules, Seaweed

Nondestructive qualitative and quantitative analysis of Yaobitong capsule using near-infrared spectroscopy in tandem with chemometrics

The purpose of the study is to present a nondestructive qualitative and quantitative approach of hard-shell capsule using near-infrared (NIR) spectroscopy combined with chemometrics. The Yaobitong capsule (YBTC) was used for demonstration of the proposed approach and the NIR spectra were collected using a handheld fiber probe (FP) without the damage of capsule shell. By comparing the differences and similarities of the NIR spectra of capsule shells, contents and intact capsules, a preliminary conclusion can be drawn that the NIR spectra contained the information of the contents. Characteristic variables were selected by competitive adaptive weighted resampling (CARS) method, and least squares support vector machine (LSSVM) method based on particle swarm optimization (PSO) algorithm was applied to the construction of quantitative models. The relative standard error of prediction (RSEP) values of five saponins including notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd were 3.240%, 5.468%, 5.303%, 5.043%, and 3.745%, respectively. In addition, for qualitative model, three different types of adulterated capsules were designed. The model established by data driven version of soft independent modeling of class analogy (DD-SIMCA) demonstrated a satisfactory result that all adulterated capsules were identified accurately after an appropriate number of principal components (PCs) were chosen. The results indicated that although the NIR spectra collection was affected by capsule shell, sufficient content information can be obtained for quantitative and qualitative analysis after combining with chemometrics. It further proved that acquired NIR spectra do contain the effective component information of the capsule. This study provided a reference for the rapid nondestructive quality analysis of traditional Chinese medicine (TCM) capsule without damaging capsule shell.