- Lipid Multiparticulate (LMP) technology offers a range of functionality applicable to many formulation challenges while also harnessing the benefits of the multiparticulate dosage format
- Dependent upon the lipid excipients utilised to form the matrix multiparticulates, LMP formulations may be designed to provide controlled release, taste-masking and/or bioavailability enhancement. The improved palatability offered with LMP formulations can also provide an optimal approach for dosing paediatrics, geriatrics and other specialised patient populations
- This workshop will present LMP technology, covering excipient options, the manufacturing process and representative case studies
Dr. Jan VertommenSenior Director Product Development and ManufacturingCapsugel
- Continuous production of water soluble granules via Twin Screw Granulation
- Smeets has developed, in collaboration with Ghent University, a technique to produce watersoluble granules containing poorly water soluble drugs of Class II (poorly soluble, highly permeable) or Class IV (poorly soluble, poorly permeable) of the Bio Classification System (BCS)
- The granulation technique – in combination with suitable excipients as polyethyleneglycols and maltodextrins – improves the extent but mainly the rate of dissolution of the poorly water soluble drug. The faster release of the API results often in an improved bioavailability and consequently a decreased intake of API to obtain the same clinical effect
- The technique can be applied for the production of human and veterinary medicines. Nowadays, the technique is used for the production of granules administered via drinking water to treat large groups of animals (poultry, pigs, …). The produced granules can also be filled in capsules or can be used as intermediates for the production of tablets
- The main advantages of the technique are the continuous process, no grinding necessary after extrusion, low temperature process (50 °C), limited problems of upscaling and the absence of solvents by which no drying step is necessary; supersaturation possible based upon formulation
Jef VerplaetseManaging Director OwnerLaboratoria Smeets
- What methodology should be used in dissolution qualification?
- Enhancing bioavailability and increasing manufacturing processes, can both be done?
- A world without injections, changing biologics paradigm
- Exploring lipid based delivery systems
TECHNOLOGY & PARTNERSHIPS
Reducing the attrition rate of New Chemical Entities (“NCE’s”) in today’s shrinking drug development pipelines has become an issue of paramount importance. A significant number of NCE’s offer therapeutic promise for patients, but exhibit limited physico-Chemical attributes for conventional, solid oral dose delivery.
Recent estimates are that as many as 40% to 50% of NCE’s are poorly water soluble and, as a consequence, prone to oral bioavailabilty problems (BCS Type II and IV). The human gastrointestinal track (“GIT”), a complex biological system, may work for, or against, a formulator’s best intensions to deliver efficacious doses of BCS Type II and IV NCE’s.
Today’s formulation scientist must have a sound working knowledge of how to develop orally-delivered, lipid-based systems that can be used advantageously to improve the bioavailability of these classes of compounds.
Vincent Plassat Scientific Affair ManagerCatalent
- Improved quality of life for cancer patients' by changing administration routes, eliminating food-effect and making dose reduction possible
- General introduction of the validated, scalable continuous flow chemistry based approach for the production of viable novel formulations from early discovery phase to cGMP production scale through a case study: cGMP production of Phase 1 Super-API formulation
- Pre-clinical Super-API formulations providing clinically meaningful benefits for the treatment of multiple myelanoma, myelogeneous leukaemia and prostate cancer
- Assessing the potential opportunity of pH independent absorption to significantly reduce the disadvantageous food effect and overall variability of compounds associated with it
- Converting parenteral cancer drugs into orally available high-value pharmaceutical Super-API products - Case study: Phase 1 Super-API formulation for the treatment of breast cancer
Genoveva FilipcseiChief Scientific OfficerDRGT
This workshop is to be attended by all delegates in Group 2
The presentation will focus on case studies using the new product range developed for customers in need of excipients with enhanced capabilities for bioavailability enhancement. The first study will focus on high productivity Hypromellose Acetate Succinate (HPMCAS) and Hypromellose (HPMC) developed for increased solids loading in solutions used to prepare spray dried dispersions. In the second part, AFFINISOL™ HPMC Hot Melt Extrusion (HME) will be highlighted using a case study where the same polymer is used in small scale spray-drying and subsequently transferred to a larger scale hot melt extrusion.
- Case study 1: High Productivity HPMCAS and HPMC polymers have significantly reduced viscosity that can result in an increase in solids loading in a spray solution by as much as 1.7-fold. In addition, high productivity polymers are capable of achieving the same level of supersaturation and nucleation inhibition as current marketed materials.
- Case study 2: AFFINISOL™ HPMC HME is capable of being used for small scale spray drying studies for formulation screening/development in purely organic solvent systems. All studied formulations successfully transferred from small scale spray drying to hot melt extrusion without reformulation.
Dr. Meinolf BrackhagenSenior ScientistDow Pharma & Food Solutions
By any measure, transdermal drug delivery (TDD) is a successful controlled release technology. Over the last 30+ years, a steady state flux of transdermal products have received regulatory approval and reached the market. For the right compound, TDD is an effective and preferred route of administration; for others, delivery across the skin makes no sense at all. Currently the “rules” that govern (passive) TDD feasibility are clearly understood. In addition to potent pharmacological activity, the transdermal candidate must be “small” of molecular weights not greater than 500 Da and with balanced lipophilicity, logP, ideally around 2 to 3.
The maximum steady state flux across the skin given by Fick´s 1st law of diffusion was predicted for 18 drugs presently approved for TDD. The predicted maximum skin flux was compared with the labeled in vivo delivery rates of the transdermal products on the market. The ratios of the in vivo delivery rates to the predicted maximum fluxes were in the range between 0.01 and 29.
For most transdermal products the ratio was within an order of magnitude of 1, which means that the transdermal systems were formulated to provide maximum thermodynamic driving force for passive diffusion across the skin. For ratios below 1, for example for Nicotine, it is clear that the delivery system itself rate controls delivery to prevent a potentially excessive exposure to the patient. The cases in which the in vivo delivery rates exceed the estimated maximum flux, can more often than not, be attributed to the presence in the patch formulation of skin penetration enhancers. However, the extent of such skin penetration enhancement is limited due to an increased incident of skin irritation. In fact, there is a direct correlation between the efficacy of an enhancer to improve permeation and its inherent ability to elicit irritation.
Nevertheless, assuming that a suitable potent drug candidate has been identified for which a convenient oral dosing regimen proves impossible (e.g., due to high first-pass effect, short biological half-life), then the feasibility of transdermal delivery requires an assessment of the compound`s skin penetrability. Predicting the candidate`s maximum skin flux can be used to evaluate whether this value is sufficient to satisfy the anticipated dose with a reasonable patch size and whether TDD is feasible.
Dr. Sandra WiedersbergR&D Project LeaderLTS Lohmann Therapie-Systeme AGGermany
technology & partnerships
- Formulation design of nano-vectors
- Commercial process development of biotech products
- Development and adaptation to pharmaceutical regulation of new manufacturing processes (nanotechnologies, amorphisation, spray drying, freeze drying
- Identification of critical steps and relevant monitoring to manufacture a product exhibiting the expected quality attribute
- Implementation of a pharmaceutical engineering tool box that will contribute to the implementation of QBD approach
- Modelling scale down and scale-up rules
- Design and set-up/qualification/validation of equipment and pilots aimed at manufacturing nanotechnology-based product
Mostafa NakachHead of Pharm Eng SanofiFrance
- Dissolution testing has been and still is the key technique when developing conventional and/or innovative formulations
- The ability of this technique to discriminate between products with different Critical Quality Attributes (CQA) is very helpful when using QbD-based development
- This approach however, can be demanding with regards to the amount of data to be generated. Hence, automation can be a great tool to achieve and overcome such demanding challenges
- Automation can add value by:
- Increaseing productivity and reducing cost per analysis
- Producing large volumes of data within a short timeframe to reduce time-to-market
- Ensuring greater safety for analysts by reducing the exposure to highly potent drugs
- The presentation will discuss the various cases, with the related automated solutions and the parameters to be considered
Samir HaddouchiManaging DirectorSPS Pharma Services
- Inorganic Controlled Release Technology (iCRT) platforms will overcome oral formulation challenges and reduce manufacturing costs
- Through fundamental control of the process parameters, drug release profiles can be tailored for purpose using iCRT (from minutes to hours from the same material)
- Control of physical properties can remove obstacles associated with solubility and bioavailability of small molecules, and allows versatility of the final form (powders, tablets, films, etc.)
- Ease of prototyping and cost-effective manufacture make inorganic carriers an excellent alternative delivery technology for generic and branded products for lifecycle management
- Partnering with technology companies with the associated know-how to control and define the optimal process for each compound has significant benefits for IP protection – patents are not always sufficient
Dr. Mark CresswellSenior Scientist, HealthcareLucideon
technology & partnerships
- Striking a balance between what is expected and what the industry/CDMO is willing to support
- Surviving the regulatory Catch-22 - balancing cost reductions with increasing regulatory demands for more measurements and analysis
- Better medicines vs. reduced costs - which do we want more?
- Deploying strategies that satisfy industry, regulatory & consumer demands
- End of the 'Perfect Therapy' - should society be expected to support an ever-ageing population or is the investment better spent elsewhere?
Tomas LandhDirectorNovo NordiskDenmark