Stabilized HME composition with small drug particles

A hot-melt extruded composition having finely divided drug-containing particles dispersed within a polymeric and/or lipophyllic carrier matrix is provided. The carrier softens or melts during hot-melt extrusion but it does not dissolve the drug-containing particles during extrusion. As a result, a majority or at least 90% wt. of the drug-containing particles in the extrudate are deaggregated during extrusion into essentially primary crystalline and/or amorphous particles. PEO is a suitable carrier material for drugs insoluble in the solid state in this carrier. Various functional excipients can be included in the carrier system to stabilize the particle size and physical state of the drug substance in either a crystalline and/or amorphous state. The carrier system is comprised of at least one thermal binder, and may also contain various functional excipients, such as: super-disintegrants, antioxidants, surfactants, wetting agents, stabilizing agents, retardants, or similar functional excipients. A hydrophilic polymer, such as hydroxypropyl methylcellulose (HPMC E15), polyvinyl alcohol (PVA), or poloxamer, and/or a surfactant, such as sodium lauryl sulfate (SLS), can be included in the composition. A process for preparing the extrudate is conducted at a temperature approximating or above the softening or melting temperature of the matrix and below the point of solubilization of drug-containing particles in the carrier system, and below the recrystallization point in the case of amorphous fine drug particles.Board of Regents, University of Texas Syste

Novel strategies for the buccal delivery of macromolecules

For years now, the delivery of small molecules through the buccal mucosal route has been described in the literature, but it has only been over the past decade that investigations into macromolecule delivery via the buccal route have sharply increased. The administration of macromolecules such as proteins and peptides, antibodies, or nucleic acids by buccal administration would be greatly enhanced due to the avoidance of the gastrointestinal conditions, rapid uptake into systemic circulation, as well as the potential for controlled drug delivery. Since macromolecules are faced with a number of specific challenges related to permeation through the epithelium, several strategies have been employed historically to improve their buccal absorption and subsequent bioavailability. Several conventional strategies to improve macromolecule penetration include the use of chemical permeation enhancers, enzyme inhibitors and the use of mucoadhesive materials acting as carriers. More recent approac

Dissolution Profiles of Lanoxin Tablets in Media Supplemented with Soluble and Insoluble Forms of Fiber

Lanoxin (digoxin) is available as 125 µg or 250 µg tablets for oral administration used to treat heart failure and arrhythmias. The objective of this study was to develop and investigate a comparativedissolutionstudy performed on lanoxin tablets in presence of insoluble or soluble forms of fiber. This study was performed to understand possible influence of fiber (psyillium husk, wheat dextrin, or powdered cellulose)on dissolutionof lanoxin in physiological relevant temperature and pH.Dissolutiontesting was performed using a USP dissolution testing apparatus II paddlerotating at 100 r/min, in 600 mL simulated gastric fluid (pH 1.2) which was maintained at (37 +/- 0.5 °C). A floating cellulose dialysis tube was used to collect sampling fractions. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Results indicate that the presence of psyillium husk in the dissolution medium hindered digoxin release. Statistical results reveal that the release profiles of digoxin in presence of wheat dextrin or powdered cellulose did not influence drug release

Dissolution Profiles of Lanoxin Tablets in Media Supplemented with Soluble and Insoluble Forms of Fiber

Lanoxin (digoxin) is available as 125 µg or 250 µg tablets for oral administration used to treat heart failure and arrhythmias. The objective of this study was to develop and investigate a comparativedissolutionstudy performed on lanoxin tablets in presence of insoluble or soluble forms of fiber. This study was performed to understand possible influence of fiber (psyillium husk, wheat dextrin, or powdered cellulose)on dissolutionof lanoxin in physiological relevant temperature and pH.Dissolutiontesting was performed using a USP dissolution testing apparatus II paddlerotating at 100 r/min, in 600 mL simulated gastric fluid (pH 1.2) which was maintained at (37 +/- 0.5 °C). A floating cellulose dialysis tube was used to collect sampling fractions. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Results indicate that the presence of psyillium husk in the dissolution medium hindered digoxin release. Statistical results reveal that the release profiles of digoxin in presence of wheat dextrin or powdered cellulose did not influence drug release

Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery

The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323 ± 8. nm particles with a high zeta potential of 32.4 ± 0.8. mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after

Stabilized HME composition with small drug particles

A hot-melt extruded composition having finely divided drug-containing particles dispersed within a polymeric and/or lipophyllic carrier matrix is provided. The carrier softens or melts during hot-melt extrusion but it does not dissolve the drug-containing particles during extrusion. As a result, a majority or at least 90% wt. of the drug-containing particles in the extrudate are deaggregated during extrusion into essentially primary crystalline and/or amorphous particles. PEO is a suitable carrier material for drugs insoluble in the solid state in this carrier. Various functional excipients can be included in the carrier system to stabilize the particle size and physical state of the drug substance in either a crystalline and/or amorphous state. The carrier system is comprised of at least one thermal binder, and may also contain various functional excipients, such as: super-disintegrants, antioxidants, surfactants, wetting agents, stabilizing agents, retardants, or similar functional excipients. A hydrophilic polymer, such as hydroxypropyl methylcellulose (HPMC E15), polyvinyl alcohol (PVA), or poloxamer, and/or a surfactant, such as sodium lauryl sulfate (SLS), can be included in the composition. A process for preparing the extrudate is conducted at a temperature approximating or above the softening or melting temperature of the matrix and below the point of solubilization of drug-containing particles in the carrier system, and below the recrystallization point in the case of amorphous fine drug particles.Board of Regents, University of Texas Syste

The effect of wet granulation on the erosion behaviour of an HPMC-lactose tablet, used as a rate-controlling component in a pulsatile drug delivery capsule formulation

The purpose of this study was to investigate the variability in the performance of a pulsatile capsule delivery system induced by wet granulation of an erodible HPMC tablet, used to seal the contents within an insoluble capsule body. Erodible tablets containing HPMC and lactose were prepared by direct compression (DC) and wet granulation (WG) techniques and used to seal the model drug propranolol inside an insoluble capsule body. Dissolution testing of capsules was performed. Physical characterisation of the tablets and powder blends used to form the tablets was undertaken using a range of experimental techniques. The wet granulations were also examined using the novel technique of microwave dielectric analysis (MDA). WG tablets eroded slower and produced longer lag-times than those prepared by DC, the greatest difference was observed with low concentrations of HPMC. No anomalous physical characteristics were detected with either the tablets or powder blends. MDA indicated water-dipole relaxation times of 2.9, 5.4 and 7.7×10−8 ms for 15, 24 and 30% HPMC concentrations, respectively, confirming that less free water was available for chain disentanglement at high concentrations. In conclusion, at low HPMC concentrations water mobility is at its greatest during the granulation process, such formulations are therefore more sensitive to processing techniques. Microwave dielectric analysis can be used to predict the degree of polymer spreading in an aqueous system, by determination of the water-dipole relaxation time

Enhanced delivery of immunosuppressive drug compositions for pulmonary delivery

The present invention includes compositions and methods for making and using a rapid dissolving, high potency, substantially amorphous nanostructured aggregate for pulmonary delivery of tacrolimus and a stabilizer matrix comprising, optionally, a polymeric or non-polymeric surfactant, a polymeric or non-polymeric saccharide or both, wherein the aggregate comprises a surface area greater than 5 m2/g as measured by BET analysis and exhibiting supersaturation for at least 0.5 hours when 11-15-times the aqueous crystalline solubility of tacrolimus is added to simulated lung fluid.Board of Regents, University of Texas Syste

Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes

© 2017, American Association of Pharmaceutical Scientists. Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the gastrointestinal tract, each has its own strengths and weaknesses that may be optimal for specific classes of compounds. Buccal and sublingual delivery enable rapid drug uptake through a relatively permeable barrier but are limited by small epithel

Inhaled Voriconazole for Prevention of Invasive Pulmonary Aspergillosis▿

Targeted airway delivery of antifungals as prophylaxis against invasive aspergillosis may lead to high lung drug concentrations while avoiding toxicities associated with systemically administered agents. We evaluated the effectiveness of aerosolizing the intravenous formulation of voriconazole as prophylaxis against invasive pulmonary aspergillosis caused by Aspergillus fumigatus in an established murine model. Inhaled voriconazole significantly improved survival and limited the extent of invasive disease, as assessed by histopathology, compared to control and amphotericin B treatments