The purpose of this column is to highlight and summarize recent key patents in the pharmaceutical arena issued by the US Patent Office in November-December, 2017.
Method of Preparing Drug Agglomerate;
PharmaDax Inc., Taiwan; P.C. Kuo, S.W. Huang and C.F. Chang; U.S. Patent # 9,833,436; December 5, 2017.
In pharmaceutical product development, particle characterization of powder materials is a very crucial aspect, which should be critically controlled within the formulating processes especially for solid oral dosage forms. The size distribution and shape of the particles affect bulk properties and processability. The present patent provides a method of preparing drug agglomerates. It involves first adding a drug powder to a solvent to form a solution, then adding a second solvent to the first solution to form a second solution. The drug powder undergoes nucleation to form drug agglomerates that are isolated from the second solution. The spherical agglomerates produced contain drug in high concentration (higher than 95% (w/w)) and the diameter ranges between 0.1 and 2.0 mm.
Wafer and Capsule Formulations with Enhanced Dissolution Rates for Fenofibrate
LTS Lohmann Therapie Systeme AG, DE; M.Li and M. Krumme; U.S. Patent # 9,849,184, December 26, 2017.
Fenofibrate is difficult to dissolve which affects its release rate in vitro. The patent describes a wafer and capsule formulations, which enhance dissolution rates for fenofibrate. The formulation comprises: fenofibrate, a surfactant, a carrier wax, a film former, a plasticizer, and optionally a super disintegrant or other ingredients. The invention also describes to the process of forming such capsules and wafers. The process of making wafer and capsule with a dosage of a BCS class II compound, is accomplished by forming a hot melt by heating together the BCS class II compound with an emulsifier and a carrier wax material; homogenizing the hot melt and adding the hot melt to an aqueous solution to form an oil-in-water (o/w) emulsion. Further, cooling the o/w emulsion followed by adding a film forming polymer, and optionally a super disintegrant, to the cooled o/w emulsion to form a liquid mass. In addition, the process also includes drying of the liquid mass to form a film and small particles for wafer and capsule, respectively.
Duloxetine Sprinkles;
Sun Pharmaceutical Industries Limited, India; R. Agarwal, T. Singhal and R. Kochhar; U.S. Patent # 9,839,626; December 12, 2017.
Since duloxetine is an acid-labile drug, it can’t be given as a liquid or chewable dosage form generally used for patients with swallowing difficulties. It is not advisable to take duloxetine orally, as it may lead to the formation of toxic degradation products in the presence of stomach acid. The patent describes a multiparticulate sprinkle dosage form comprising enteric coated discrete units of duloxetine hydrochloride that can be mixed with or sprinkled on food and swallowed intact with the food. The dosage forms have higher acid resistance as compared to existing delayed release capsules but at the same time are bioequivalent. A multiparticulate sprinkle dosage form comprising a plurality of discrete units, wherein each unit included: a drug layered subunit comprising an inert core, and a drug layer surrounding the inert core, wherein the drug layer comprises duloxetine or a pharmaceutically acceptable salt.
Dose-Dumping Resistant Controlled Release Dosage Form;
Osmotica Kereskedelmi Es Szolgaltato KFT, HU; H.D. Benedetti, C.R. Franco, G.S. Bigatti, J. Faour and A.C. Pastini; U.S. Patent # 9,827,234; November 28, 2017.
This patent invention pertains to a delivery device for the controlled delivery of methylphenidate (MPH), wherein the dosage form exhibits improved resistance to alcohol-related dosedumping. It overcomes some of the disadvantages by providing a controlled release oral dosage form comprising a core of one abusable drug (e.g. MPH), one pharmaceutical excipient, and a coating surrounding the core, wherein the dosage form exhibits reduced ethanol-related dose-dumping in vitro when placed in an aqueous alcohol solution. The controlled release oral dosage form is an osmotic device. It exhibits less than 1.5 fold ethanol related increase in total amount of abusable drug. This drug is released from the core during first 120 min after placement in aqueous environment compared to the drug release rates in 0.1N HCl and in 40% ethanol + 0.1N HCl.
Multimodal Antimicrobial Therapy;
Longhorn Vaccines and Diagnostics, US; G.W. Fischer and R.F. Schuman; U.S. Patent # 9,814,766; November 14, 2017.
Staphylococcus aureus (SA) is a major cause of severe infections, which may rapidly progress from a mild local infection to sepsis and multi-organ system failure. Lysostaphin is an effective agent for treating SA infections where it attacks the Staphylococcal bacterial cells. This invention is directed to compositions and methods for preventing and/or treating disorders caused by nonStaphylococcal microorganisms using lysostaphin. The cell walls of microbes such as M. tuberculosis (MTB) are very different from SA and many antibiotics that are effective for treating SA infections do not work well for treating MTB. The compositions and methods contain lysostaphin, altered forms of lysostaphin and synergistic combinations of lysostaphin with an enzyme, antibiotic and/or antibody treatment. The lysostaphin is administered to the lungs as aerosolized nanoparticles (size ranging from 1-3 µm or less) at a dose of 5 pg to 0.5 mg of lysostaphin/kg of patient weight.
Biomarker Specific Amphiphilic Nanoparticles;
University-Industry Foundation, Yonsei University, Korea; S. Haam, Y.M. Huh, J.S. Suh, J. Yang, H.O. Kim, J. Choi, E. Jang, B. Kang, I. Noh, and S.R. Bae; U.S. Patent # 9,815,945; November 14, 2017.
The present invention relates to amphiphilic nanoparticles as a poly amino acid-based nanoplatform having a targeting ability specific to a biomarker. The present invention provides an amphiphilic nanoparticle including: a block copolymer containing a hydrophilic polymer and a hydrophobic polymer (A); and a block copolymer containing a peptide cleaved by a proteolytic enzyme and a hydrophobic polymer (B). The amphiphilic nanoparticle of the claimed invention is to be used as a diagnostic or therapeutic drug or gene carrier. It works by forming a self-assembly through the balance of hydrophobic and hydrophilic molecules. This assembly is selectively recognized by a proteolytic enzyme specifically expressed in a cellular membrane of a specific cell, by a peptide cleaved by the proteolytic enzyme and then being selectively cleaved by the proteolytic enzyme to transfer a diagnosis reagent, drug, or gene to the cells. The amphiphilic nanoparticle is in the form of polymersomes or micelles with average particle diameter of 50 to 200 nm.
Method for Delivering Gonadotropin Releasing Hormone into a Lumen of the Intestinal Tract;
Rani Therapeutics, LLC, US; M. Imran; U.S. Patent # 9,808,510; November 7, 2017.
Gonadotropin releasing hormone (GnRH) analogs are useful for the treatment of prostate cancer but require parenteral administration. The current patent describes an oral delivery of GnRH in a capsule form. The drug is delivered in the intestinal wall with the help of a tissue penetrating member after oral ingestion of the capsule. The tissue penetrating member is within the capsule, but in the next configuration, it is advanced out of the capsule and into the intestinal wall. The solid dosage of GnRH delivered into the intestinal wall is comprised of biodegradable material (PGLA and a sugar). The most important aspect of this system is the Tmax value. The drug release is very fast from this device.