Magnus N. Hattrem

Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD.

The effect of filler particles on the texture of food gels

Abstract Food gels usually consist of a large range of ingredients, including solubilised material, aggregated particles, dispersed air bubbles and/or immiscible liquids distributed throughout the finalised product. The presence of a discontinuous phase can strongly influence the textural and sensory properties of food gels, and the interactions between the filler particles and the polymer matrix are of especial importance. At the end of this chapter, a case study is included for gelatin-based gelled emulsions, highlighting different aspects influencing the rheological properties of filled gels through experimental examples.

Investigation of Physico-Chemical Properties of Gelatin Matrices in Correlation with Dissolution Studies

Gelatin is a versatile biopolymer obtained from a partial hydrolysis of collagen. Gelatin is commonly used in formulation of pharmaceuticals and nutraceuticals, encapsulating the active ingredient. For these applications the dissolution profile of the matrix in the gastrointestinal tract (GIT) is of crucial importance. The dissolution of a gelatin matrix in the GIT may be seen as a two-step procedure: gel-sol transition of the gelatin network, followed by diffusion of the peptide strands from the concentrated matrix to the bulk liquid. Thus, it is clear that the melting temperature is important in gelatin gel dissolution investigations. Depending on the raw material (bovine or porcine sources) and extraction conditions, gelatins with wide variations in molecular size distribution – and therefore varying rheological properties/melting temperatures – may be obtained. Dissolution studies are generally time consuming and therefore it would be advantageous to predict the dissolution profile without performing in vitro measurements. The scope of this work was to evaluate if any of the physico-chemical properties of the gelatin matrices can be used to predict the dissolution profiles of the gelatin gels.

Soft, chewable gelatin-based pharmaceutical oral formulations: a technical approach

Abstract Objective: Hard tablets and capsules for oral drug delivery cause problems for people experiencing dysphagia. This work describes the formulation and properties of a gelatin based, self-preserved, and soft chewable tablet as an alternative and novel drug delivery format. Materials and methods: Gelatin (8.8–10% in 24.7–29% water) constituted the matrix of the soft, semi-solid tablets. Three different pharmaceuticals (Ibuprofen 10%, Acetaminophen 15%, and Meloxicam 1.5%) were tested in this formulation. Microbial stability was controlled by lowering the water activity with a mixture of sorbitol and xylitol (45.6–55%). Rheological properties were tested applying small strain oscillation measurements. Taste masking of ibuprofen soft-chew tablets was achieved by keeping the ibuprofen insoluble at pH 4.5 and keeping the processing temperature below the crystalline-to-amorphous transition temperature. Results: Soft-chew formulations showed good stability for all three pharmaceuticals (up to 24 months), and the ibuprofen containing formulation exhibited comparable dissolution to a standard oral tablet as well as good microbial stability. The rheological properties of the ibuprofen/gelatin formulation had the fingerprint of a true gelatin gel, albeit higher moduli, and melting temperature. Conclusions: The results suggest that easy-to-swallow and well taste-masked soft chewable tablet formulations with extended shelf life are within reach for several active pharmaceutical ingredients (APIs).

The Relative Bioavailability of Ibuprofen After Administration With a Novel Soft Chewable Drug Formulation

The first aim of the present study was to evaluate the bioavailability of ibuprofen dispersed in a novel soft chewable formulation compared with a traditional ibuprofen tablet; its second was to map the quality of taste masking and patient product satisfaction. In a phase 1, single‐center, open‐label, randomized, crossover study, healthy subjects received a soft‐chew formulation or a hard tablet (reference), both containing 100 mg ibuprofen. Serial blood samples were collected over 24 hours to assess ibuprofen bioavailability. Taste and satisfaction after chewing the novel formulation 3 or 8 times were evaluated with a questionnaire. The soft‐chew formulation showed comparable bioavailability to the reference tablet. The highest peak plasma concentration was observed after 3 chews, and the relative bioavailability was approximately 8% higher compared to 8 chews. The overall flavor was well appreciated, and chewing 3 times was significantly preferred (P = .043) over chewing 8 times. Soft chewable drug formulations may improve compliance and potentially benefit several subpopulations who experience dysphagia.