The purpose of this column is to highlight and summarize recent key patents in the pharmaceutical arena issued by the US Patent Office in February 2019.
Suspensions of Cyclosporin A Form 2; A.V. Gore, P.S. Mohanty, and E.Q. Farnes; Allergan, Inc., USA; U.S. Patent # 10,206,971, February 19, 2019.
Cyclosporin A is available in the market as an ophthalmic emulsion under the brand name Restasis. It is indicated to increase tear production in the treatment of dry eyes. Due to cyclosporine A’s poor water solubility, it is currently formulated by dissolving it in oil or by using high levels of surfactants and solubilizers. The former leads to forming an emulsion and the later forms an aqueous solution of cyclosporine. The inventors of the present invention discloses a nanosuspension formulation of cyclosporine A using its crystalline polymorph. This invention may provide a better dosage form of cyclosporine A. The inventors claim that the nanosuspension may have advantages such as higher bioavailability, longer retention time in eye, improved tolerability etc. over the current formulations.
Orally Disintegrating Tablet Formulation for Enhanced Bioavailability; J. Djordjevic, M.M. Bommana, W. Phuapradit, N.H. Shah, and C.A. Pizzo; Kashiv Pharma, USA; U.S. Patent # 10,195,150; February 5, 2019.
An orally disintegrating tablet (“ODT”) dosage form has certain important requirements in addition to the proper disintegration times. The perception that rapid disintegration leads to rapid rates of absorption and bioavailability does not hold true with poorly water-soluble drugs. Therefore, following dosage form disintegration, it still is necessary for the drug to dissolve before it can be absorbed. It would be advantageous to simultaneously provide rapid disintegration and a drug solubility enhancement in a dosage form. This patent invention gives a formulation comprising of an amorphous solid dispersion or a mixture of a poorly water-soluble drug and an ionic polymer, which exhibits fast disintegration of tablet and enhanced dissolution/bioavailability. The ionic polymer is present in an amount so as to maintain the poorly water -soluble drug in a substantially amorphous form and disintegrate the tablet within 30 seconds.
Packaging System for Oxygen- Sensitive Drugs T. Devouassoux, E. Forat, and J.K. Proctor; Fresenius Kabi Deutschland GmbH, DE; U.S. Patent # 10,214,338; February 26, 2019.
Present invention provides a packaging system for oxygen sensitive drugs in injectable dosage form. It claims to prevent degradation of drugs by oxidation. In pharmaceutical development, oxygen sensitive drugs and their formulations require additional development to prevent degradation during manufacturing and storage. The packaging system disclosed in the patent uses a syringe with a cap to accommodate the oxygen sensitive drug. The syringe is hermetically sealed in a blister pack with an oxygen absorber. The inventors claim that the packaging may realize zero percent oxygen levels in the blister and syringe for at least a year.
Three-Component-Multistage Malaria Vaccine; H. Spiegel, A. Boes, G. Edgue, V. Beiss, M. Sack, A. Reimann, and R. Fischer; Fraunhofer-Gesellschaft zur Foerderung der angewandten Forschung, DE; U.S. Patent # 10,213,501; February 26, 2019.
Most vaccines are produced to target a single antigen only. Producing a successful vaccine against malarial parasites is challenging because of its complex and multistage life cycle. Depending on the developmental stage, the parasite displays different sets of surface antigens, which exhibit extensive sequence polymorphism that helps them evade an immune response. The present invention provides novel and improved multicomponent, multi-stage vaccines composed of different recombinant proteins, comprising several different Plasmodium falciparum antigens from the pre-erythrocytic, the blood, and the sexual parasite main stages.
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Topical Tetracycline Compositions; D. Tamarkin, E. Gazal, I. Papiashvili, Y. Hazot, D. Schuz, and R. Keynan; Foamix Pharmaceutical, USA; U.S. Patent # 10,213,512; February 26, 2019.
Tetracyclines are broad-spectrum antibiotics, which are used orally for the treatment of dermatological conditions, such as acne and rosacea. However, despite their high therapeutic value, tetracyclines are very unstable and incompatible with many formulation excipients like water, protic substances and oxidizing agents. This patent relates to oleaginous gel formulations, foamable formulations and foams comprising tetracycline, which are stable. A topical therapeutic hydrophobic breakable composition includes a carrier comprising 60%-99% (by weight) of one or more hydrophobic oil, one or more viscosity-modifying agents selected from the group of fatty alcohol, fatty acid and wax and a tetracycline antibiotic, where a part of the tetracycline antibiotic is suspended in the composition. The viscosity of the composition is ≈ 30% higher than that of the carrier without the tetracycline antibiotic. Tetracycline is chemically stable in the composition for at least six months where > 90% of the tetracycline does not break down. This composition is packaged as a breakable foam that breaks easily upon application of shear force.
Salts and Prodrugs of 1-methyl-D-tryptophan; M. Mautino, S. Kumar, F. Jaipuri, J. Waldo, H. Potturi, and H. Zhuang; NewLink Generics, USA; U.S. Patent #10,207,990; February 19, 2019.
Indoximod is 1-methyl D-tryptophan. IDO1 (indoleamine-2,3-dioxygenase) catalyzes the degradation of tryptophan (Trp) into kynurenines, which plays an important role in the regulation of immune responses by triggering anergy (absence of the normal immune response to a particular antigen or allergen) on reactive effector T cells and by modulating diff erentiation and activation of regulatory T cells (Treg). Indoximod has been demonstrated to relieve IDO-mediated immunosuppression in vitro and in vivo. Indoximod is orally bioavailable and provides satisfactory pharmacokinetic parameters up to 800 mg/dose, which produces Cmax value of 15 μM. However, the PK profile is non-linear above this dose. One needs Cmax value of 20 μM or higher for therapeutic activity. By using the salts and prodrugs of Indoximod, the linearity of PK profi le was shown to extend to higher doses.
Dry Powder Compositions with Magnesium Stearate; K. Yadidi; Otitopic, USA; U.S. Patent # 10,195,147; February 5, 2019.
Magnesium stearate (MgST) is the magnesium salt of stearic acid. It is widely used in the production of nutraceuticals and pharmaceuticals. MgST is known to catalyze acid-based hydrolysis often causing incompatabilities with active pharmaceutical ingredients (APIs) susceptible to acid-based hydrolysis such as non-steroidal anti-inflammatory drugs (NSAID), e.g., acetylsalicylic acid (ASA). The present invention discloses a stable dry powder composition for inhalation, which includes ASA and stearate. This inhaled route of drug administration provides fast and efficient treatment for reducing the risk of a thromboembolic event. Formulation contains dry particles with mass median aerodynamic diameter in a range of about 1 μm to about 5 μm.