Adare Pharmaceuticals. A partnership that adds value to your products

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2 Adare Pharmaceuticals Adare Pharmaceuticals provides enhanced medicines, creating new possibilities for improved patient health. Our vision to expand Building upon our legacy, we strive to reshape medicines tailored to the needs of the evolving global healthcare market. Through internal development and the acquisition of new technologies and products, we will expand our pipeline and capabilities to deliver greater value to partners and patients. A heritage that adds value For decades, we have solved complex formulation, manufacturing and commercialization challenges, resulting in transformational medicines that deliver value to all our stakeholders. Unparalleled expertise We see opportunities for transforming medicines where others cannot because of our proprietary technologies, as well as our employees expertise and experience in R&D, manufacturing complex products and commercialization. A wealth of resources More than ever before, we have the vision, resources and talent, making the company uniquely suited to unlock the potential of more medicines, helping patients to maximize the benefit of their treatments. Our global presence A partnership that adds value to your products From the laboratory, to clinical trials, to market placing a higher emphasis on drug delivery strategies can help differentiate your products in a crowded pharmaceutical environment and maximize your opportunities for success. We create new possibilities by: Adding value to your products through life-cycle management Combining multiple technologies for customized drug delivery Identifying opportunities to accelerate product development timelines Leveraging brand loyalty through improved adherence and flexibility Offering IP protection or extending patent life through application of our proprietary technologies We will ensure a protected pathway to commercialization for your products Broad portfolio of proven oral technologies Formulation expertise for novel clinical results Patent protection for enhanced market position Guidance and support to maximize regulatory exclusivity Worldwide commercialization Vandalia, Ohio, USA Mont-Saint-Hilaire, Quebec, Canada Lawrenceville, New Jersey, USA Houdan, France San Giuliano, Milan, Italy Pessano, Milan, Italy Since 2009, our partners have commercialized more than 40 products worldwide. To learn more about our transformative partnerships, please contact Lisa Miller at Lisa.Miller@adarepharma.com for North America inquiries, for outside North America inquiries, or visit 3

3 transformative opportunities In Pharmaceutical Technology SM Technology Platforms Flexible. Effective. Proven. Our proprietary platform technologies can create an oral delivery medication that improves efficacy and safety, while encouraging patient adherence. Platform Technology Attribute Taste Masking and ODTs Technologies to improve taste and provide alternative dosage forms AdvaTab Liquitard Microcaps High dose, IR, and/or customized release Robust tablets ODTs, RDTs, powder for extemporaneous suspensions, and sprinkles for ease of administration Effective taste masking Patient-friendly, ideal for those who experience difficulty swallowing regular capsules and tablets Convenient, portable dosage forms Taste Masking and ODTs Customized Drug Release Bioavailability Enhancement From formulation challenges to proprietary product solutions Customized Drug Release Technologies to optimize therapeutic performance Diffucaps Diffutab Eurand Minitabs Orbexa TM Customized drug-release profiles to optimize efficacy, safety, and dosing frequency Delivery systems can be created for challenging drugs exhibiting extreme ph-dependent solubility profiles Multiple formulations of the same drug or different drugs, each formulation exhibiting a unique release profile. Can be combined in a single dosage form Adare Pharmaceuticals develops and manufactures value-added pharmaceutical products based on its broad range of proprietary oral drug delivery technologies, including taste masking and orally disintegrating tablets (ODTs), customized drug release, and bioavailability enhancement. Bioavailability Enhancement Technologies to improve solubility Biorise TM Diffucaps Enables the development of viable formulations of drugs with limited solubility Solid solution, hot-melt extrusion (HME), and spray-drying capabilities also available IR=immediate release; RDT=rapidly disintegrating tablet. 5

4 Taste Masking and ODTs Patient adherence to prescribed therapy is widely recognized as a significant issue. Several factors, such as bitter taste, administration difficulty, dosing frequency, and inconvenience, are attributed to the lack of patient acceptance and adherence to a prescribed regimen. Our proprietary technologies address these challenges by: Improving taste: Effectively masking the bitter taste of many active pharmaceutical ingredients (APIs) Promoting ease of administration: For anyone who has difficulty swallowing tablets and capsules, especially pediatric, geriatric, and dysphagic patients Adding convenience: Making medications easy to transport and easy to swallow, without the need for water Technologies to improve taste and provide alternative dosage forms Microcaps Taste Masking Technology This technology achieves a uniform and efficient drug particle (crystal, granulate, or liquid) coating and may enhance overall patient adherence by improving the product s acceptability. In fact, Microcaps technology is commercialized in over 20 countries. Advantages of Microcaps Taste Masking Technology Effective taste masking while achieving rapid dissolution by incorporating gastrosoluble pore-former(s) Multiple dosage form options Smooth, pleasant mouthfeel with no aftertaste Encourages patient adherence Immediate or customized release profiles Ability to directly coat crystals, liquids, or granules AdvaTab Orally Disintegrating Tablets Available in versatile dosage forms ODTs have been formulated in dosage strengths up to 500 mg Chewable tablets RDTs facilitate delivery of higherdosage strengths of up to 1500 mg Sprinkles, dry sachets, and stick packs Powder for extemporaneous suspensions AdvaTab tablets incorporate coated or partially coated drug particles that are uniformly dispersed in a low-moisture, rapidly disintegrating matrix. Each ODT is formulated to achieve an acceptable taste, a disintegration time of 30 seconds or less according to the FDA s Guidance for Industry: Orally Disintegrating Tablets, and desired release profile. Additionally, AdvaTab enables rapid disintegration in the mouth without water. AdvaTab tablets have been formulated to be bioequivalent to IR RLDs. Polymer Membrane Drug Particle Pore-Former Technology How Microcaps Taste Masking Technology works Microencapsulation technology employs versatile and precise coating techniques to encapsulate individual drug particles. This process uses coacervation (ie, phase separation) and can also incorporate a spray-coating process, creating polymeric membranes of varying degrees of porosity and thickness to completely encapsulate drug-containing particles. The membrane improves taste by forming a barrier between the drug and taste buds in the mouth. How Pore-Former Technology works The taste masking membrane may comprise at least one gastrosoluble organic, inorganic, or polymeric pore-former. The gastrosoluble pore-former of the taste masking membrane, being insoluble at saliva ph, provides effective taste masking when placed in the oral cavity; however, the pore-former rapidly dissolves upon entry into the stomach for rapid release of the drug from coated/ taste masked drug particles, thereby enhancing the probability of success in achieving bioequivalence to an immediate release (IR) reference listed drug (RLD). Advantages of AdvaTab Orally Disintegrating Tablets Ideal for patients who have difficulty swallowing, especially pediatric, geriatric, and dysphagic patients Opportunity to combine AdvaTab with Microcaps and Diffucaps to create IR or controlled-release ODTs Can be used in a variety of therapeutic areas, such as oncology, pain, CNS, and gastrointestinal (GI) Robust tablets are suitable for multiple-packaging configurations, including push-through blister packs Patented manufacturing process and formulations High drug-loading capability up to 500 mg Microcaps 7

5 Taste Masking and ODTs (cont) Liquitard Technology Liquitard provides an effective and convenient dosage form for patients who have difficulty swallowing tablets or capsules, as is often the case with pediatric and geriatric patients. In addition to a wide range of flavors, Liquitard can be mixed with or sprinkled on easy-to-swallow foods to further improve convenience of administration. Customized Drug Release Adare offers a variety of technologies to customize drug-release profiles. These profiles can be combined to improve efficacy, enhance safety, and reduce dosing frequency resulting in improved convenience and increased patient acceptability. Our range of drug-release profiles includes: Single-dose Stick Pack Timed sustained release: Achieves therapeutic effect by maintaining drug levels over a period of time, while reducing the side effects associated with peak plasma concentrations Timed Sustained Release Release Sustained Time Rapid onset with extended release: Enables immediate pulse of a portion of the active ingredient, while the remainder is released over an extended time period Release Immediate Pulse Immediate Pulse Time Microcaps stick pack shown actual size. How Liquitard Technology works This technology is formulated to create extemporaneous suspensions that facilitate the administration of drug particles (crystal, granulate, or liquid) that can be filled into a single-dose stick pack (sachet). When poured into water, coated drug particles and additional excipients (ie, suspending agents, flavors, sweeteners) produce a ready-touse suspension. This unique technology can be combined with Microcaps technology, incorporating the benefits of taste masking. Advantages of Liquitard Technology Improves patient convenience and adherence Allows easy administration of high doses Provides accurate dosing Enhances portability via single-dose packaging Timed pulsatile release: Enables the drug to be released in pulses or waves, separated by defined time intervals Timed Pulsatile Release Delayed release: Allows the delayed onset of drug release (ie, minimizes drug release in the stomach and rapidly delivers the drug upon exposure to a certain ph in the GI tract) Chronotherapeutic release: Facilitates drug delivery at time intervals that coincide with changes in biorhythms, such as circadian rhythm Time Targeted delivery: Targets drug release in specific regions of the GI tract, optimizing drug absorption and efficacy Release Delay Pulse 9

6 Customized Drug Release (cont) Technologies to optimize therapeutic performance Diffucaps Customized Release Technology This technology has the flexibility to incorporate functional, release-controlling polymers or protective coatings onto drug-layered cores, granules, or crystals. This multiparticulate system provides sophisticated control of drug delivery and optimizes release profiles for single drugs and drug combinations. Examples of customized release particles Diffucaps (Organic Acid or Alkaline Buffer) Solubility-Modulation Technology Many weakly basic drugs exhibit ph-dependent solubility profiles. Some weakly basic drugs are extremely soluble in physiological fluids (ie, solubility >500 mg/ml over the ph range of 1-8 and practically insoluble at a ph 8), making it difficult to achieve a prolonged release profile. Further, other weakly basic drugs are moderately soluble at a ph 4 but are poorly soluble or practically insoluble at a ph 6. Certain other weakly basic drugs are practically insoluble at all physiological phs. Diffucaps technology can be used to customize the release profiles of drugs demonstrating varying solubility profiles at physiological phs. Inert Core Material Polymer Timed Erosion Polymer Timed Erosion Polymer Organic Acid Drug Substance Controlled-Release Outer Coating Alkaline Buffer Drug Substance Drug Substance Immediate Pulse Sustained-Release Polymer Timed Sustained Release How Diffucaps Customized Release Technology works A drug core (granulated or layered onto a neutral surface) is created, followed by the application of one or more rate-controlling, functional polymer membranes. The drug-layering process can be conducted from either aqueous or organic solvent based drug solutions/ suspensions and results in a small (approximately 1.5 mm or less in diameter), spherical, multilayered bead. Advantages of Diffucaps Customized Release Technology Permits easy adjustment of both dosage strength and dissolution profile to achieve the desired in vivo pharmacokinetic (PK) profile Beads can have different release profiles, different active ingredients, or both all in one product Can be used in combination with other proprietary technologies to enhance drug solubility in certain sections of the GI tract Reduces gastric mucosal irritation Available as a capsule, ODT, RDT, or as a sprinkle Can minimize food effect Seal-Coat Polymer Timed Pulsatile Release Our proprietary technologies can be combined to deliver unique ODT or RDT formulations Sustained- Release Layer Organic Acid Diffucaps Bead Inert Particle Core Alkaline Buffer Diffucaps Bead Seal-Coat Polymer How Diffucaps Solubility-Modulation Technology works An optimal ph microenvironment is created within the coated bead. For drugs that are practically insoluble at a ph 6, an acidic microenvironment is created by incorporating an organic acid layer in order to solubilize and release the drug for systemic absorption. For drugs with extreme solubility at physiological phs, a basic microenvironment is created by incorporating an alkaline buffer layer to reduce solubility, thereby prolonging its release. Furthermore, the organic acid layer is placed underneath the drug layer while the alkaline buffer is placed over the drug layer and coated with one or more functional polymers in order to ensure that the organic acid or the alkaline buffer is not depleted until release of the drug is complete. Microcaps Taste Masking Technology Diffucaps Customized Release Technology 11

7 Customized Drug Release (cont) Eurand Minitabs Controlled Release Technology This technology combines the simplicity of a tablet formulation with the flexibility of multiparticulate dosage forms with high drug-loading capability. A significant advantage of Eurand Minitabs technology is the ability for the patient or caregiver to open the capsule and sprinkle the contents on soft foods or add to a liquid. This is especially helpful for the pediatric patient, the elderly patient, or anyone who has difficulty swallowing. Patient-centric approach features easier-to-swallow formulations Minitab 2.0 mm Microtab 1.5 mm MiniMicrotab 1.2 mm Ultra MiniMicrotab 1.0 mm 6+ months 6 months 4+ months 4 months Capsule Release-Control Polymer Diffutab Customized Release Technology This technology provides sustained release and targeted delivery of pharmaceutical products. Particularly useful in the development of high-dose products, Diffutab is an effective way to develop sustained-release dosage forms for once-daily administration. Mini Tablet (Granulation or Hydrophilic Matrix) Optional Film or Functional Polymer Coating How Eurand Minitabs Controlled Release Technology works Tiny cylindrical tablets ( 2 mm in diameter) are created and functional membranes are applied to further control release rates. Because of their small size, Eurand Minitabs can be filled into capsules or sachets as final dosage forms. This facilitates the development of combination products that offer two or more drugs or release profiles within a single capsule. Eurand Minitabs can also utilize Diffutab Customized Release Technology, allowing for even greater flexibility in designing a release profile. Advantages of Eurand Minitabs Controlled Release Technology Combination tablet and multiparticulate dosage form High drug-loading capability Wide range of customized release profiles Flexible dosage form (capsules, sachets, or sprinkles) may improve patient adherence Drug Polymer How Diffutab Customized Release Technology works A blend of hydrophilic and hydrophobic polymers are combined to control drug release via diffusion through, and erosion of, a matrix tablet, which can be coated with one or more functional polymers. Advantages of Diffutab Customized Release Technology High drug-loading capability Wide range of customized release profiles, including zero-order release 13

8 Bioavailability Enhancement The bioavailability of a drug is strongly dependent on its solubility in the aqueous environment of the GI tract. Solubility is one key determinant among several biopharmaceutical properties that influence the speed of onset of action, the variability of absorption between patients, and any food effect variation. Technologies to improve solubility Our two distinct, patented, proprietary technologies Biorise TM and Diffucaps (Solid-Solution or Solid-Dispersion) enhance bioavailability of drugs that are poorly soluble at physiological phs. In addition, we have the capacity to apply HME and spray-drying techniques to enhance solubility. Biorise TM Bioavailability Enhancement Technology This technology creates new physical entities (NPEs) with better solubility profiles. These NPEs are produced by breaking down the crystalline drug into nanocrystals and/or amorphous (non-crystalline) drug particles that are stabilized in a carrier system to maintain the drug in its activated form for the duration of its shelf life. Biorise NPEs Creating NPEs Two distinct proprietary activation systems are available to create NPEs high-energy mechano-chemical activation (HEMA) and solvent-induced activation (SIA). These systems convert drugs to their stabilized, thermodynamically activated state. Additionally, they provide flexibility and enable the technology to be applied to a range of compounds with different characteristics. Key drug characteristics are reviewed. For example: One of two activation systems is selected Process converts drug to highly stabilized form Process results in final dosage forms No solubility in the solvent Solid State HEMA Some solubility in the solvent Liquid State SIA Powder that can be incorporated into capsules or tablets Fully Nanocrystalline Mixed Nanocrystalline and Amorphous Fully Amorphous Diffucaps (Solid-Solution or Solid-Dispersion) Bioavailability Enhancement Technology In this application, Diffucaps technology enables the development of novel, solubilityenhanced, amorphous, solid-solution/solid-dispersion formulations of drugs that exhibit poor solubility in physiological fluids. As previously discussed, Diffucaps is a multiparticulate bead system made up of multiple layers of drug, excipients, and release-controlling polymers. The beads can contain a solidsolution/solid-dispersion drug form and crystallization inhibitor to enhance bioavailability by maintaining the drug in its amorphous state. The solubility-enhanced beads can be coated with one or more functional polymers to achieve extended-release profiles suitable for onceor twice-daily dosing regimens. Polymeric Network Nanocrystal Molecular Cluster in Amorphous Phase Spatial Constraints This approach transforms the original crystalline form of the drug into an amorphous and/or nanocrystalline, thermodynamically activated solid form characterized by higher solubility thereby enhancing the rate and extent of absorption in the GI tract. Advantages of Biorise TM Bioavailability Enhancement Technology Can be applied to class II compounds with solubilities in the range of <10 to 500 µg/ml May provide a faster onset of action, equivalent therapy at lower doses, and/or oral dosing of poorly soluble drugs, as well as reduced food effect for poorly soluble drugs 15

9 A PARTNERSHIP THAT S TRULY TRANSFORMATIVE SM Adare Pharmaceuticals provides enhanced medicines, creating new possibilities for improved patient health. Enhance and protect the value of your portfolio with our proprietary technologies Eight distinct oral formulation technologies, including taste-masking, bioavailability enhancement, and customized drug release Ability to create novel products and facilitate life-cycle management Technologies that are applicable to Rx and OTC products Opportunity to maximize ROI with product-specific patents All technology platforms are scaled-up, commercially validated worldwide, and provide IP protection Contact one of our licensing representatives today! North America inquiries: Lisa.Miller@adarepharma.com Outside North America inquiries: Visit us at Locations Adare Pharmaceuticals, Inc. Princeton Pike Corporate Center 1200 Lenox Drive, Suite 100 Lawrenceville, New Jersey USA Adare Pharmaceuticals, Inc. 845 Center Drive Vandalia, Ohio USA Adare Pharmatech Canada, ULC 597, Boul. Laurier Mont-Saint-Hilaire, QC, Canada, J3H 6C4 Adare Pharmaceuticals S.r.l. Via Martin Luther King, Pessano con Bornago (MI) Italy Adare Pharmaceuticals S.r.l. Via Molise, San Giuliano Milanese (MI) Italy Adare Pharmaceuticals SAS La Prévôté - Route de Bû Houdan France All service marks are property of Adare Pharmaceuticals, Inc. ADVATAB is a registered trademark of Adare Pharmaceuticals, Inc. LIQUITARD, MICROCAPS, DIFFUCAPS, DIFFUTAB, and EURAND MINITABS are registered trademarks of Adare Pharmaceuticals S.r.l. BIORISE and ORBEXA are trademarks of Adare Pharmaceuticals S.r.l Adare Pharmaceuticals, Inc.