DRUG DEVELOPMENT ACCELERATING TIME TO MARKET

Drug Development - Accelerating time to market PHARMACEUTICAL DEVELOPMENT Discovering and developing drugs is becoming a progressively expensive, high-risk venture and pharmaceutical development has less resource from which increased productivity is expected. However, the supply of novel pharmaceuticals should know no limits; the molecular and formulation permutations are infinite. It is these endless possibilities that drive Malvern to provide the tools to accelerate development and formulation of the most demanding molecules into successful medicines. Accelerating Drug Development Malvern’s...

THE CHALLENGE: TO DEVELOP MORE DIFFERENTIATED DRUG PRODUCTS, FASTER DEVELOPMENT STAGES • Target Identification & Validation MOLECULE DISCOVERY • Drug Discovery • Compound Management • Toxicity Screening COMPOUND ATTRITION • Lead Optimization • Structure-Activity Relationship (SAR) MOLECULE OPTIMIZATION Phase I-III CHEMICAL DEVELOPMENT • Active • Pilot Plant Pharmaceutical • Crystallization Ingredient (API) • Particle • Process Engineering Research and • Process Safety Development FORMULATION DEVELOPMENT • Stability • "Processability" • Bioavailability/ Bioequivalence (BA/BE) • "Scaleability"...

Drug Development - Accelerating time to market ACCELERATING DRUG DEVELOPMENT: THE MALVERN TOOLBOX The particle size distribution of active ingredients, excipients, granules and droplets is an important physical characteristic of the materials used to create pharmaceutical products that have the right Quality Target Product Profile. It can affect product performance, manufacturing scale up, processability and stability of the final drug formulation. Key performance parameters such as dissolution, absorption rates and content uniformity can all be affected by the particle size distribution of various...

Particle properties – such as size, size distribution, zeta potential and shape influence the bulk rheological properties of a variety of formulated products. Characterizing the rheological properties of materials plays a crucial role in drug product performance from the stability of suspensions containing Active Pharmaceutical Ingredients (APIs), to the delivery and application characteristics of creams and ointments for product efficacy, to the optimized properties of high performance excipients for tablet coatings. When particulate matter is small then other light scattering techniques may...

Drug Development - Accelerating time to market MOLECULE DISCOVERY Effective Compound Library Management: Rapid and accurate screening Screening chemical compounds for activity High throughput screening of large libraries of chemical compounds is the dominant technique used in early stage drug discovery. However, when screening lead compounds for activity, the true potential of new leads can become masked by the presence of nonspecific or ‘promiscuous’ inhibitors. Often, the mechanism of inhibition is through aggregation of compound molecules and is concentration dependent. The challenge is to...

MOLECULE OPTIMIZATION Getting NCEs to pre-clinical trials faster Optimization of new chemical entities Approximately 90% of new chemical entities (NCEs) discovered today are poorly soluble, which creates a major challenge for efficient drug development. In order to rapidly evaluate such compounds at the preclinical stage, the drug candidate is often dosed orally as an aqueous-based suspension. In order to monitor efficacy of the suspension accurately, administering trial drug candidates in this form requires accurate, repeatable and validatable control of the active ingredient’s particle size,...

Drug Development - Accelerating time to market CHEMICAL DEVELOPMENT Automate bioavailability and bioequivalence studies Optimization and bioequivalence When characterizing bioavailability or bioequivalence of nasally administered drugs, in support of (New Drug Application) NDAs or (Abbreviated New Drug Application) ANDAs, for nasal aerosols and sprays, the United States Food and Drug Administration (FDA) recommends several tests. In cases where the active component or components are suspensions, one important attribute is the drug particle size distribution. The challenges of this particular...

FORMULATION DEVELOPMENT Controlling liposome formulation drug delivery Controlling liposome formulation The size of a liposomal vesicle plays a pivotal role in the pharmacokinetic and pharmacodynamic attributes of chemotherapeutic drugs, whereby the liposome acts as a carrier of the drug to the site of action. The challenge is accurate and rapid measurement of the size of liposomes, on very limited amounts of sample, at the formulation concentration and under physiological conditions. This is necessary to ensure effective drug delivery systems that do not aggregate, allowing the best vesicle...

Drug Development - Accelerating time to market FORMULATION DEVELOPMENT Getting the depot and enteric formulation right first time Formulation Development Polymer excipients are widely used in parenteral and oral solid dosage forms. The degree of polymerization (DP) determines the polymer’s performance for a given action. Whether it is used to protect, sustain the release of, or make site specific, the active ingredients, the challenge is accurate determination of the number average molecular weight, weight average molecular weight and the polydispersity. Triple-Detection Size Exclusion Chromatography...

FORMULATION DEVELOPMENT Optimizing tablet coating processes Optimizing tablet coatings The uniformity with which a tablet coating is applied to a core is highly dependent on the rheological characteristics of the film coating itself. The liquid spray coating has a finite time from landing on the tablet surface, to level and join the rest of the coating before it dries. The time-dependent rheological response, or thixotropy of the coating material, after passing through a spray nozzle onto an Oral Solid Dose (OSD) such as tablet, is a key element in process understanding. The conditions of a tablet...