New Patent: MannKind Scientists stay on the cutting edge

[mnholdem]

August 4, 2016

Source: patentscope.wipo.int/search/en/detail.jsf?docId=US175565191&recNum=1&maxRec=780&office=&prevFilter=&sortOption=Pub+Date+Desc&queryString=FP%3A%28MANNKIND%29&tab=PCTDescription

Highlights:

The present invention provides methods for the synthesis of diketopiperazines using the catalyst phosphorus pentoxide to achieve...

• faster reaction times
• higher yields
• higher purity
• shorter reaction times

...over that of conventional step(s)/method(s). 

Other benefits:

• Diketopiperazines can be formed into particles that incorporate a drug;
• The combination of a drug and a diketopiperazine can impart improved drug stability and can be administered by various routes of administration;
• As dry powders these particles can be delivered to specific areas of the respiratory system, depending on particle size;
• The particles can be made small enough for incorporation into intravenous suspension dosage forms;
• Oral delivery is also possible using a suspension, or as particles pressed into tablets or contained in a capsule.
• These diketopiperazines can also facilitate absorption of the associated drug.

"It is an object of the present invention to provide improved methods of synthesis for diketopiperazines. These 2,5-diketopiperazines have been shown to be useful in drug delivery, particularly those bearing acidic R groups."

[cm5]

More:  www.google.com/patents/US9241903

Methods are provided for drying a particle. Specifically, there is provided a spray-dried diketopiperazine-insulin particle formulation having improved aerodynamic performance and in which the active agent is more stabile and efficiently delivered as compared to that of the lyophilized diketopiperazine-insulin formulation. The dry powders have utility as pharmaceutical formulations for pulmonary delivery.

Publication number US9241903 B2
Inventors Bryan R. Wilson, Marshall Grant
Original Assignee Mannkind Corporation

The success of any pharmaceutic particle depends not only on its efficacy in treating a disease or condition, but also having superior pharmaceutic properties over other known therapeutics. Desirable pharmaceutic properties sought in a dry powder particle include improved aerodynamics, pharmacodynamics and stability. However, producing particles with such properties is an ongoing challenge in the art. One approach to achieving this aim in the art, lies in the methodology used to manufacture particles.

Thus, the present invention provides the novel and unexpected discovery that the pharmaceutic properties of the dry powder can be generally improved by using spray drying in preference to lyophilization to remove solvent from the particles.

Surprisingly, the density of the spray-dried particles was roughly twice that of freeze-dried particles. This can be advantageous in providing higher doses. Dry powder inhalers generally impose a limit on the volume of powder, and thus the dosage of active agent, that can be delivered in a single operation. A powder of higher density, but at least similar respirable fraction, allows larger doses to be administered in a single operation, rather than requiring more operations per dose, formulations with higher % loading of active agent, or alternate inhaler or inhaler cartridge designs to accommodate various volumes of powder.

Active agents contemplated for use in the compositions and methods described herein may include any polymer or large organic molecules, most preferably peptides and proteins. Examples include synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and nucleic acid sequences, having therapeutic, prophylactic, or diagnostic activities. Active agents may also include small molecules and vitamins. An active agent of the present invention may also be a vasoactive agent, a neuroactive agent, a hormone, an agent regulating metabolism, weight, or blood glucose levels, an anticoagulant, an immunomodulating agent, a cytotoxic agent, an antibiotic, an antiviral, an antisense molecule, or an antibody.