1,721,025 research outputs found
ORAL DELIVERY SYSTEMS INTENDED FOR COLONIC RELEASE OF INSULIN AND SELECTED FUNCTIONAL ADJUVANTS
No full textAbstract of the PhD thesis entitled “Oral delivery systems intended for colonic release of insulin and selected functional adjuvants”
Colon delivery has gained increased attention as a potential approach to improve the oral bioavailability of peptides and proteins. In this respect, the suitability of a previously developed release platform (ChronotopicTM) was explored for the conveyance of insulin and selected functional adjuvants. The system consists of a drug core and a swellable/erodible hydroxypropyl methylcellulose (HPMC) release-controlling coating. When an outer enteric film is applied, colon delivery is obtained based on relatively consistent small intestinal transit time. Preliminarily, the compatibility of insulin with a protease inhibitor (camostat mesilate, CM) and an absorption enhancer (sodium glycocholate, NaGly) was assessed. Subsequently, differing insulin/adjuvants release patterns were pursued by properly modifying the system formulation. A concurrent liberation of these compounds was achieved after reproducible and programmable lag phases from devices in which the protein and enzyme inhibitor/absorption enhancer were included in the core unit. The possibility of timing the adjuvant release to occur prior to that of the protein, which might allow a more favorable environment to be established in advance, was then investigated. For this purpose, prototypes with a CM/NaGly interlayer enclosed between HPMC coatings with differing thicknesses were prepared that elicited flexible two-pulse release profiles
Design and Evaluation of Oral Delivery Systems Intended for Colonic Release of Insulin and Selected Functional Adjuvants
No full textPreparation and evaluation of formulations obtained by hot melt extrusion containing an inhibitor of the p-glycoprotein (p-gp) efflux pump
No full textBiphasic multicomponent pharmaceutical dosage forms containing substances able to modify the partitioning of drugs
No full textThe present invention refers to a drug multicomponent biphasical composition that enables to solve the problems of prior art
In vitro release of heparin from polyester films intended for intravascular treatment of restenosis
No full textTransport characteristics of a beta sheet breaker peptide across excised bovine nasal mucosa
No full textThe purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na2EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro.The effective permeability coefficient (Peff) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 ± 0.44)*10-5, while in the presence of sodium caprate (0.5%) a Peff of (9.58 ± 1.82)*10-5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na2EDTA > poly-l-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na2EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4°C compared to 37°C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport.The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease. Copyrigh
Evaluation of Bovine Insulin Compatibility with Protease Inhibitor and Absorption Enhancer Compounds for an Oral Colon Delivery System
No full textPurpose.
In view of developing an insulin-containing oral colon delivery system, the compatibility of the protein with selected protease
inhibitor and absorption enhancer compounds, i.e. camostat mesilate (CM) and sodium glycocholate (NaGly), was assessed.
An HPLC evaluation of insulin and its main degradation products, namely A21-desamido insulin (A21), Other Insulin
Related Compounds (OIRC) and High Molecular Weight Proteins (HMWP), was carried out. Thermal analyses were also
performed to support the chromatographic investigation.
Methods.
Insulin-CM, insulin-NaGly (both 1:10 by weight) and insulin-CM-NaGly (1:5:10 by weight) physical mixtures were prepared
and stored for a one-year period in glass vials at 4°C. HPLC analyses were performed at 0, 1, 2, 3, 6 and 12 months according
to Eur. Ph. 6th Ed. For the DSC study, insulin and CM or NaGly mixtures, in which the protein amount ranged between 0 and
100%, were weighed in aluminium pans that were subsequently sealed and perforated. Analyses were immediately performed
under 70 mL/min nitrogen purge at the heating rate of 10°C/min.
Results.
Insulin content did not vary in any sample type throughout the study period, whereas all assayed degradation products tended
to increase slightly. However, none exceeded the limits set by Eur. Ph. 6th Ed. for raw bovine insulin (3% for A21 and OIRC,
1% for HMWP). As far as calorimetric analyses are concerned, the melting temperature and heat of fusion of CM were not
affected by increasing amounts of protein in insulin-CM mixtures. Indeed, a linear relationship was found between the
melting enthalpy of CM and its percentage in the mixtures. With respect to NaGly, which is in the form of a hydrate, the
crystallization event following water loss was considered. No shift in the crystallization temperature was noticed, and the
relevant enthalpy was shown to increase as a linear function of its percentage in the mixtures.
Conclusion.
The overall results indicated that the selected adjuvants could be included in an insulin solid formulation intended for oral
colon delivery without having a significant impact on the protein stability
Colon Delivery of Insulin : Assessment of the Protein Compatibility with Protease Inhibitor and Absorption Enhancer Compounds
No full textSystem for the colon delivery of drugs subject to enzyme degradation and/or poorly absorbed in the gastrointestinal tract
No full textSaid invention refers to a pharmaceutical form for selective colon delivery of drugs or bioactive molecules degraded and/or poorly absorbed in the gastrointestinal tract. The system comprises a core consisting of the active ingredient, and a protease inhibitor layer and/or an absorption enhancer layer, said core being separated from these layers by means of a polymer that swells and/or dissolves and/or is degraded when in contact with the biological fluids present in the gastro-intestinal tract; depending on the thickness of the polymeric layer, the release of the drug can be modulated with respect to the inhibitor and/or promoter
In Vivo Performance of an Oral Swellable/Erodible Multiple-Unit Delivery System for Pulsatile and Time-Dependent Colonic Release
No full text- …
