The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study

Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps® HPMC capsules, Vcaps® Plus HPMC capsules, gelatin and DRcaps® designed release capsules were used. The three HPMC-based capsules (Vcaps®, Vcaps® Plus and DRcaps® capsules) were tested as single capsules; furthermore, seven DUOCAP® capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and 13C3) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP® capsule-in-capsule configuration using a DRcaps® designed release capsule within a DRcaps® designed release outer capsule. In this combination, the inner DRcaps® designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps® Plus HPMC capsules showed the fastest and most consistent disintegration.

Stability and In Vitro Aerodynamic Studies of Inhalation Powders Containing Ciprofloxacin Hydrochloride Applying Different DPI Capsule Types

In the case of capsule-based dry powder inhalation systems (DPIs), the selection of the appropriate capsule is important. The use of gelatin, gelatin-PEG, and HPMC capsules has become widespread in marketed capsule-based DPIs. We aimed to perform a stability test according to the ICH guideline in the above-mentioned three capsule types. The results of the novel combined formulated microcomposite were more favorable than those of the carrier-free formulation for all capsule types. The use of HPMC capsules results in the greatest stability and thus the best in vitro aerodynamic results for both DPI powders after six months. This can be explained by the fact that the residual solvent content (RSC) of the capsules differs. Under the applied conditions the RSC of the HPMC capsule decreased the least and remained within the optimal range, thus becoming less fragmented, which was reflected in the RSC, structure and morphology of the particles, as well as in the in vitro aerodynamic results (there was a difference of approximately 10% in the lung deposition results). During pharmaceutical dosage form developments, emphasis should be placed in the case of DPIs on determining which capsule type will be used for specific formulations.

In Vitro Evaluation of Enteric-Coated HPMC Capsules—Effect of Formulation Factors on Product Performance

A comparative study on different enteric-coated hard capsules was performed. The influence of different formulation factors like choice of enteric polymer, triethyl citrate (TEC) concentration (plasticizer), talc concentrations (anti-tacking agent), and different coating process parameters on the sealing performance of the capsule and the disintegration time were investigated. Furthermore, the influence of different disintegration test methods (with disc vs. without disc and 50 mM U.S. Pharmacopoeia (USP) buffer pH 6.8 vs. biopredictive 15 mM phosphate buffer pH 6.5) was evaluated. All formulations showed sufficient but not equivalent acid resistance when tested. Polymer type was the main factor influencing the capsule sealing and disintegration time. In addition, TEC and talc could affect the performance of the formulation. Regarding the choice of the disintegration test method, the presence of a disc had for the most part only limited influence on the results. The choice of disintegration buffer was found to be important in identifying differences between the formulations.

Formulation of Lipoprotein Microencapsulated Beadlets by Ionic Complexes in Algae-Based Carbohydrates

The present study aims to produce sustained-release algae-based carbohydrate microbeadlets of lipoproteins rich-in carotenoids extracted from organic sea buckthorn fruits. β-carotene represented the major compound of the lipoproteins extracts. Emulsification and algae-based carbohydrates, such as sodium-alginate and kappa-carrageenan, provide an inert environment, allowing the embedded targeted bioactive compounds—lipoproteins rich in carotenoids in our case—to maintain greater biological activity and to have a better shelf life. Furthermore, the microbeadlets prepared from sodium-alginate–kappa-carrageenan (0.75%:0.75% w/v) crosslinked with calcium ions showing 90% encapsulation efficiency have been utilized in HPMC capsules using beadlets-in-a-capsule technology, to use as a delivery system for the finished product. The GI simulated tests performed under laboratory conditions suggested that the sodium-alginate–kappa–carrageenan combination could be useful for the formulation-controlled release of microbeadlets containing lipoproteins rich in carotenoids.

Evaluation of capsule labelling for its wall contents as gelatin or non gelatin

Background: Capsules are the most commonly used solid drug dosage form and are made up of gelatin or non gelatin. Currently the gelatin based capsules drug formulations are more used. However, current issue of vegetarian and non vegetarian capsules has come up due to recent Indian government initiative to promote vegetarian capsules.Methods: There were 100 capsule dosage forms were examined for the gelatin or HPMC wall contents and nature of medicine contained in capsules, whether ayurvedic or allopathic.Results: Out of 100 capsules studied 55 had gelatin wall base while 25 had HPMC and 20 capsule labels did not mention the nature of capsule wall constituent. Out of 55 gelatin capsules 30 were of allopathic while 25 capsules were of ayurvedic medicines. Among HPMC, 15 were ayurvedic while 10 allopathic. 20 capsules had no mention of its constituent and among these non labelled capsule formulations had 11 from ayurvedic and 9 from allopathic medicines.Conclusions: The current study revealed that gelatin capsules forms bulk in Indian market. Even the gelatin capsules contained ayurvedic medicines while 10% of HPMC capsules contained allopathic medicines. Non labelled capsules formed 20% of total capsules. These findings suggest wider scope for promotion of HPMC based capsules.

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

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