What are some current critical industry issues that have made drug delivery such a hot topic?
Shaukat Ali, PhD, Technical Support Manager, Pharma Solutions, BASF Corporation: The industry is adopting modern and more innovative formulation technologies to overcome the challenges with delivery of (i) poorly soluble drugs (amorphous dispersion versus emulsions/nanoparticles) (ii) oral delivery of peptides and proteins (iii) controlled release of opioids (iv) abuse deterrent or tamper resistance formulations (v) cytotoxic drugs via liposomes or nanoparticles, (vi) taste-masking of bitter drugs amongst others. In addition, the launches of biologics are on the rise, and the industry is taking aim at finding the appropriate technologies and polymeric excipients for delivery of those molecules to minimize adverse effects. Though many of the biologics are destined for parenteral IV and infusion, the industry is on the lookout for novel excipients and polymers that deliver robust and stable formulations with higher drug loading and encapsulation efficiency. Moreover, as formulation challenges continue to rise with the advent of new chemical entities (NCEs), excipient manufactures are developing new and novel excipients that meet the industry’s small and large molecule formulation requirements.
Ronak Savla, Scientific Affairs Manager, Catalent Pharma Solutions: Creating safe, effective, and patient-friendly drugs is the crux of drug development. An increasing percentage of the small molecule pharmaceutical pipeline is composed of poorly soluble drugs that are highly targeted but have inflated molecular weight and high lipophilicity. These properties lead to poor bioavailability, and possibly attrition, due to lack efficacy or safety concerns. Drug delivery technologies have the potential to overcome attrition by improving the solubility and in turn, bioavailability. Another driver of increased drug delivery usage is the drugs that benefit from being formulated to have modified release characteristics, which can reduce dosing frequency and improve patient adherence.
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The number of biologic molecules in development continues to claim a larger share of the total pharmaceutical pipeline. Drug delivery technologies are critical to formulating biologic drugs that require high doses and those that will be self-injected by the patient.
Dan Dobry, Director, Commercial Development, Lonza Pharma & Biotech: As the pharmaceutical industry develops a better understanding of biological targets, the variety of drug molecules needed to hit these targets becomes increasingly diverse. Examples include poorly soluble molecules, such as very high melting or highly lipophilic compounds that need oral bioavailability enhancement, and poorly permeable or large-molecular weight molecules that are not orally absorbed with standard technology.
A number of other factors contribute to the continuing industry focus on drug delivery, including:
- Patient-centric care and personalized therapeutics that call for complex delivery requirements from dosage forms and devices;
- Increased use of multiparticulate technologies to create oral solid pediatric-specific formulations;
- The ongoing abuse of pain relief medications and stimulants, requiring sophisticated abuse-deterrent formulations that can still meet the target product profile required;
- The NDA 505(b)2 regulatory pathway for improving or repurposing existing compounds, which often necessitates fixed dose combinations.
Dr. Finn Bauer, MBA, Global Head of Solid Formulations R&D at MilliporeSigma: In past decades, the manufacture of solid formulations was dominated by mass production. With trends toward regionalization and personalization of treatment approaches, the industry needs faster, more efficient and increasingly flexible solutions. At the same time, the market situation is challenging: NMEs in the pipeline are faced with unfavorable odds such as poor solubility, tighter regulatory scrutiny and building cost pressure. This has resulted in a neck-to-neck race under severe pressure to bring a successful formulation to market. Drug delivery and specialty excipient technologies can help overcome these hurdles.
Hibreniguss Terefe Ph.D., V. P. Research & Development, ExxPharma Therapeutics LLC: The pipelines of developmental drugs are getting richer due to the scientific advances of the past decade, however, along with it came about enormous drug delivery challenges. Some examples are listed below.
- Low solubility drug candidates: Poorly soluble drug substances often result into low and varying intrinsic bioavailability which in turn lead to development of suboptimal drug products, prolong the overall development process, and even attrition of the drug candidates from the pipeline. The net effect is they contribute to the increasing cost of drug development.
- Delivery of macromolecules derived from biotechnology arena: Significant strides have been made during the last decade or so in the discovery of pharmacologically effective large molecules which currently account for about 39% of all drug candidates in the pipeline. These molecules pose significant drug delivery challenges and are drawing the attention of many formulation scientists.
- Patent expiration of brand drug products: The high cost of drug development has forced companies to develop a business strategy that necessitated implementation of life cycle management that prolong patent life by improving the efficacy, safety and compliance of existing medicines. Innovative drug delivery technologies that improve product performance and provide market exclusivity are in high demand.
- The opioid epidemic: Opioid abuse and misuse has become a very serious public health issue that is detrimentally affecting societies. As a result, the FDA and other stakeholders are trying to combat the problem through multifaceted strategies. One of the strategies which many pharmaceutical companies are working on is the development of abuse deterrent drug delivery technologies.
Can you tell us about some new drug delivery technologies and/or processes that are helping pharmaceutical companies bring new products to market or are reviving older products? Is there a specific process or technology that you see as most effective?
Ali: New technologies that are helping tackle today’s drug delivery challenges encompass the non-conventional such as hot melt extrusion, spray drying, electro-spraying/spinning, Kinetisol, and lipid-based self-emulsifying drug delivery systems in soft gel and hard gel capsules. Other technologies such as immediate release and controlled release are being used to benefit both the patient with reduced dosing that leads to improved compliance, and the drug marketer, by providing life cycle management options. Selecting the appropriate technology to innovate formulations for life cycle management requires excipients (polymers or solubilizers) to increase solubility and bioavailability, controlling their abilities for timely on set controlled delivery through polymer coating technology, drug layering of pellets or minitablets, and fast dissolving ODTs for pediatric and geriatric populations. Others include taste-masking technology for effective delivery of bitter APIs by mitigating side effects without infringing on intellectual properties.
Savla: Newer technologies such as 3D printing have proven commercial capabilities in certain instances, but they are yet to be widely validated and applied. These technologies work at lab-scale, but present challenges for GMP manufacturing, and are extremely difficult to scale up, lack necessary process controls, and have high manufacturing costs. The potential incremental increase in solubility or other benefits offered by these newer technologies is not yet of sufficient increase to offset the additional work and time needed. Nanotechnology continues to be touted as the next greatest drug delivery technology. Whether we should consider that nanotechnology has been truly successful in the drug delivery space is debated among prominent researchers in the field. However, several approved drugs (injectables) have been formulated using liposomal technology.
Salt forms, lipid-based drug delivery systems, hot melt extrusion, and spray drying are time tested and proven oral small molecule drug delivery technologies. Anyone would be hard pressed to justify bypassing these technologies and going straight to a novel technology to address the biopharmaceutical challenges of their drug molecule. No specific process or technology can be said to be most effective. Each technology has different characteristics including mechanism of action and unique aspects in which they can help or not. It is impossible to say that one technology is the most effective.
Dobry: Over the last decade, the large number of insoluble and poorly permeable molecules has led to significant advancements in the understanding of bioavailability enhancement technologies, including amorphous dispersions, lipid suspensions/emulsions, micronization/nanosizing and salts/co-crystals, such as lipophilic salts. In addition, specific patient profiles and targeted routes of delivery have driven advances in particle engineering, such as functional multi-particles for taste-masking or engineered particles for inhalation delivery.
In terms of modified release technology, a single dosage form can combine modified release and bioavailability enhancement and also enable sustained release where the drug needs enhancement for colonic absorption. In addition, enteric protection allows delivery of sensitive molecules such as proteins and microbiome actives to the lower gastrointestinal tract without gastric exposure. Bioavailability enhancing technologies can also offer an approach to improving existing compounds or repurposing drugs via the NDA 505(b)2 pathway.
Some technologies stand out as more broadly applicable and their range continues to expand as process, formulation and excipient understanding advance. For example, amorphous dispersions for solubility challenges can be used to deliver “brick dust” compounds, which have very high melting points and low solubility in both aqueous and organic systems – and are increasingly prevalent in the drug development pipeline. Solid dispersion technology innovations regarding the use of temperature, processing aids and customized equipment are being successfully utilized to advance these compounds, many of which would have previously been discarded due to processing or delivery challenges.
Bauer: It is important to realize that there is no one-size-fits-all approach. The individual path forward strongly depends on the API characteristics, the final formulation type and administration route as well as the desired or available manufacturing process. This is why it is critical that formulators have multiple options available to choose from.
Looking at the needs for increasingly flexible and more efficient operations, continuous pharmaceutical manufacturing processes are a very prominent field of development. Tighter process controls and a more thorough process and product understanding drive both quality and flexibility improvements. Looking ahead, additive manufacturing processes like 3D pill printing – today still in its infancy – will substantially change technologies and processes mid to long-term. In the here and now, however, solubility enhancement is one of the most pressing challenges. Here we see a strong trend towards technologies that modify the physical nature of the API rather than changing the drug molecule chemistry. Technologies like drug carriers and hot melt extrusion do exactly this by enabling stable amorphous formulations that increase the apparent solubility of the API while keeping its chemical nature unchanged.
Terefe: The pharmaceutical industry continuously invests a lot of resources to develop drug delivery technologies that enable development of new products and enhance the performance of approved drug products using innovative technologies, such as ExxPharma’s, comprising of solubility enhancement, modified release, abuse deterrence and fixed dose combination products. Given the number of poorly soluble drug substances in discovery pipelines as well as among approved products, Solubility enhancement has become the go-to drug delivery technology to improve the clinical viability of new molecular entities and develop line extensions and product enhancements of existing drug products.
Currently, there are many solubility enhancement technologies that are practiced in the industry. Out of these technologies, amorphous solid dispersions (ASD) have been increasingly gaining in popularity. Since early 1990s, several drug products which contain ASDs that were prepared using solvent-based and non-solvent based manufacturing processes have been approved by FDA.
The most popular technologies that are used to manufacture amorphous solid dispersions are spray drying (SD) and hot melt extrusion (HME). Since each poorly soluble drug exhibits unique physicochemical properties that pose a variety of formulation and processing challenges, applying only a single ASD manufacturing technology across a spectrum of poorly soluble drugs is impossible.
ExxPharma has therefore devoted a lot of resources to expand and perfect the application of HME in the development of its proprietary solubility enhancement platform DisExx™ through an API-specific formulation and process design. DisExx™ is applicable to all poorly soluble drug substances irrespective of their physicochemical properties.
How have functional excipients/raw materials helped with drug delivery? Are these excipients becoming more important as solubility concerns arise?
Ali: Highly functional excipients play an important role in overcoming solubility and bioavailability challenges that arise from APIs having higher melting points and/or higher log P. For example, lipid-based emulsifiers such as Kolliphor® RH40, HS15, EL, P188 and P407 among others, have increasingly been used in the design and development of effective delivery systems for potent drugs by solubilization in micelles and stabilization of nanoparticles. Likewise, polymer excipients such as Kollidon® VA64, K-30 and Soluplus® are employed to enhance bioavailability by maintaining supersaturation of the API in the GI tract by uptake of oral dosages.
Savla: As the number of new chemical entities with solubility concerns continues to increase, so does the importance of functional excipients. Excipients have evolved to be ingredients with uses beyond simply bulking. Functional excipients help overcome solubility, permeability, and stability issues. An excellent example of functional ingredients is those used in lipidbased drug delivery systems (LBDDS). The combination of oils, glycerides, and surfactants function to be digested or are self-emulsifying to increase solubility of drugs. Another example is polymers used in amorphous solid dispersion (spray drying or hot melt extrusion) to help get spring-and-parachute effect and keep a drug in an amorphous state to reach supersaturation levels and retard recrystallization.
Dobry: Many drug delivery technologies are highly dependent on formulating with enabling excipients to modify the API properties to achieve the desired delivery target.
In inhalation, excipients often act as a diluent to enable dose uniformity from the delivery device and as a matrix that provides the ability to engineer stable respirable particles.
In modified release, the properties of the formulation excipients are critical to controlling the API’s release from the dosage form based on a range of mechanisms, from diffusion to erosion to PH-triggered dissolution.
For bioavailability enhancement, functional excipients play a key role in manufacture, stability and performance (absorption). This includes acting as a processing aid, stabilizing the amorphous solid state and also forming highly active drug polymer species in vivo that supply free drug for absorption.
Bauer: Excipients are the backbone of a formulation. In the past, for example, the role of excipients was often reduced to fillers and binders in solid formulations. The availability of a suitable excipient, however, is a prerequisite for a successful drug delivery approach. Take for example hot melt extrusion – simply said, it would not be possible to apply this drug delivery technology without a thermostable matrix excipient (or without a plasticizer that helps to reduce the required process temperature). Today’s innovations in this field reach even further. New polymers for HME aim to offer multiple functionalities like stabilization of the solid amorphous form in the tablet and inhibition of drug precipitation in dissolution.
Another example of a functional excipient is silica drug carriers. These functionalized particles allow for API adsorption onto their surface and into their pores, stabilizing the drug in a better soluble amorphous form.
But functionality of excipients is also very relevant for more classical approaches to drug formulation such as direct compression. Without a filler of excellent flowability, compressibility and uniformity the direct compression of especially very high and low dose formulation would not be possible.
Terefe: Functional excipients are critical components of any drug delivery system, and must be selected judiciously. Regulatory requirements coupled with physicochemical properties that pose processability, compatibility or stability issues limit the number of excipients that could be used, for instance, for solubility enhancement purposes.
Recognizing the need to expand the number of functional excipients suitable for solubility enhancement, excipient manufacturers are not only coming up with new excipients but also with improved functionalities of existing excipients. These include:
- BASF’s Soluplus® is a new functional excipient that was developed to enhance solubility of poorly soluble drug substances during hot melt extrusion.
- Dow Chemicals has introduced Affinisol® systems, i.e. HPMC and HPMCAS grades that have improved thermal properties for successful HME processing.
- Evonik is expanding the application of Eudragit® polymers for hot melt extrusion applications.
- Gattefosse is offering a range of pharmaceutical excipients that could be used in the development of lipid based and selfemulsifying drug delivery systems.
While these inventions are very important, it may not be sufficient to use individual excipients to solve all formulation and processing issues. Appropriate combinations of multiple excipients processed under specific conditions may help overcome many of the issues. ExxPharma has been able to successfully maximize the benefits of approved pharmaceutical excipients by designing unique formulations consisting of multiple excipients that provide synergetic functionalities.
As drug delivery issues become more commonplace – what is the role of suppliers to industry? How important is their product/formulation experience to the success of any given product?
Ali: The role of excipient suppliers is to help the industry overcome formulation challenges in a more efficient and timely manner. These challenges range from poor solubility/bioavailability, to taste-masking bitter APIs, to deterring abuse of a drug by controlling its release, to managing the lifecycle of a drug and more. Moving forward, closer partnerships will become even more important as new manufacturing technologies with the promise of improved efficiency (e.g., continuous manufacturing and 3D printing), may impact excipient functionalities and performance in unforeseen ways. The industry seeks to partner with excipient suppliers that have a science-based approach to gaining insight and understanding on this.
Savla: Excipient suppliers are becoming a more integral part of the drug development process. They provide a wealth of knowledge about their products. New excipients are critical to evolving current delivery technologies and ushering in innovative technologies and processes. Suppliers are increasingly conducting proactive research projects to demonstrate function and activity and safety of their excipients. These studies also can serve as proof-of-concept and help understand which types of molecules can benefit from the novel excipients. Co-processed excipients that are commonly used together can save time and money.
Dobry: As the technologies needed for specific drug delivery challenges become more specialized, individual sponsor companies are increasingly looking to development and manufacturing partners with specific expertise to find solutions to their problem statements. Service providers must be able to partner with customers across the design, development and manufacturing continuum. Much of the early-stage drug pipeline is in the hands of emerging and small biopharma companies, which require not only partnership for access to enabling technologies but also broad support across development and manufacturing.
Partnership therefore includes offering innovative formulation design, the ability to rapidly progress the product through clinical development with a commercially relevant product profile and ultimately supply of the product via a business model that is customizable to the supply challenges unique to each product’s patient population and global distribution demands. Phase-appropriate processing is critical, especially in rapidly screening, advancing and scaling promising compounds. Additionally, having the appropriate capabilities for containment and isolation at all stages is required, given the increasing percentage of highly potent compounds under development.
Finding external partners with experience in successfully utilizing and scaling specialized enabling technologies to advance complex molecules is critical. An understanding of the regulatory landscape is also required for effective external partnerships, especially for global product launches. Experienced regulatory services can help ensure that unnecessary bioequivalence studies that often accompany tech transfers for enabling formulations are avoided.
Bauer: It is critical for a supplier to have thorough formulation expertise to be able to understand customers’ challenges and develop products that help bring final drug products to market efficiently. This includes a combination of both detailed regulatory understanding and technical expertise. Because compendial specifications of excipients often focus on physicochemical characteristics and purity, particle engineering can be applied to develop fully compendial excipients with new functionality.
So, particle engineering of excipients to design specific functionality is one role where suppliers step in. Another very important role is the application and regulatory support of these excipients. Application expertise and support ensure that functionally optimized products will be leveraged to their full potential. Regulatory support fosters an efficient approval process. Both types of support are banked on an in-depth excipient understanding that suppliers have established during product development.
Terefe: For successful product development, the supplier should have not only knowledge and experience in solving drug delivery issues, but also good understanding about the regulatory requirement throughout the product development phases. As every drug substance is unique, the development process should be guided by good science. A cost-effective, phase-appropriate development plan that shortens development time is crucial, especially for small discovery companies that operate in funding constrained environment, which requires wide-ranging product and formulation development experience. It is absolutely essential to have a thorough understanding about the interplay between formulation variables and processing parameters to successfully develop high quality drug products. ExxPharma, as an innovation-driven CDMO, has utilized its extensive experience in formulation design and manufacturing science to develop innovative products for clients that address bioavailability enhancement, food effect, dose reduction, pill burden, dosing frequency and abuse deterrence. ExxPharma provides comprehensive product development services from preclinical to Phase III.
If a company is having drug delivery/solubility problems with a product in development is there a “checklist” of items/steps, based on the latest technologies that they need to review before shelving a product?
Ali: Not one size fits all. The industry is taking a more holistic approach to screen all the new chemical entities (NCEs) coming out of discovery by using high throughput (HT) technologies such as Pion’s Sirius Inform for measuring solubility in bio-relevant media. This is important for identifying the appropriate excipients, polymers and lipids-based surfactants for the development and/or selection of one formulation technology versus others. It also depends on the dosage form and strength. For instance, the selection of an amorphous solid dispersions versus self-emulsifying (SEDDS/SMEEDS) is often determined by robustness of formulation for efficient delivery to meet the required dosage strengths but is also determined by the faster go-to-market approach, which is often dictated or empowered by the contract research organizations’ (CROs/CMOs) internal capabilities and expertise. For example, a CRO with expertise in softgel, might be interested to identify the excipients compatible to liquid fill in softgels including Kolliphor® EL, RH40, HS15, Kollisolv® PEG300, PEG400 among others; while, CROs with expertise in solid dispersions, might be able to derive the oral tablet formulations requiring the excipients for solid dispersions, such as Kollidon® VA64, Kollidon® 30, Soluplus®, Kollicoat® MAE100-55 among others.
Savla: Companies should set realistic expectations and understand what is needed to achieve efficacy and safety endpoints. The first step is to complete a thorough preformulation screening study (salt form and polymorph screening, solubilities in solvents, excipients, buffers, and biorelevant media, and stability studies). Catalent uses the Developability Classification System (DCS) to understand what hurdles are impacting drug absorption (permeability and solubility). The information from these studies helps guide proper formulation and drug delivery development, and ensure that developmental risks (e.g., poor absorption, food effects, stability, changes in physical forms) are known and addressed. For drugs with low solubility, LBDDS and amorphous solid dispersions are leading choices. The most promising technologies should be assessed in parallel to save time and ensure a data driven decision. Performing physiologically-based pharmacokinetic (PBPK) modelling is highly beneficial. It can reveal how different parameters influence bioavailability and if the drug is subject to extensive hepatic first-pass effect. Catalent also classifies drugs according to other classification systems to characterize drug distribution and excretion.
Dobry: Rather than a checklist, this could be referred to as more of a science-based decision-tree or flowchart. A prerequisite is having the key enabling technologies in place, along with the phase-appropriate processing and the relevant expertise and track record for each technology. Technology optimization is not about trying all the technologies in a boxchecking exercise; it’s about understanding the delivery problem and optimizing the technology best suited to address it.
The first key step is identifying the dose for the therapeutic need. For a given API, the challenges can increase as the dose increases. Next, clearly identify the right problem statement, such as a solubility vs. permeability vs. metabolism-driven delivery challenge. Last, in order to solve that problem, all the key physical properties relating to biorelevant delivery in various forms (crystalline, amorphous and solution/dispersions states) must be quantified.
All of this information is often needed to select the right problem statement to optimize the formulation performance. For example, in bioavailability enhancement, is our biggest challenge to address dissolution rate, extent of dissolution or sustainment of dissolution? For this assessment, companies also need the appropriate in vitro characterization tools and in vivo testing plan.
Bauer: There are numerous approaches for solubility enhancement which are typically classified into chemical and physical approaches. An example for a chemical approach would be to choose a different salt form of an API which shows better solubility properties. This, however, usually is only applicable to the very early stages of NME developments. At later stages in product development, physical approaches such as micronization, formulation of amorphous solid dispersions or the application of drug carriers are the method of choice.
Typically, companies review first the technologies readily available inhouse – due to profound expertise and the availability of specialized equipment. Often the number of implemented, enabling technologies is limited to a few core capabilities. Moving beyond the established in-house capabilities, companies most frequently reach out to highly specialized CDMOs for technical evaluation and validation of alternative approaches. Based on the available in-house technologies and existing cooperation networks with specialized CDMOs, “checklist” will be very individually differing between companies.
Terefe: Understanding physicochemical and biopharmaceutical properties of a drug substance is the first step to successful drug product development. Having exhaustive pre-formulation studies and determining BCS classifications help to plan and prioritize which technologies and formulations to consider. Relevant questions include: Is the poor solubility crystal lattice energy-limited or solvation-limited? Does the drug exhibit high melting point and high hydrophobicity? What is the propensity of the drug to recrystallize once converted into amorphous form? Computational methods that use molecular modeling and solubility parameters are helpful to select appropriate carrier polymers for the development of amorphous solid dispersions.
Depending on the physicochemical properties of the drug substances, the most appropriate technologies with appropriate formulations shall be rationally selected. Having a tool kit of different technologies to address solubility issues irrespective of their physicochemical properties is key to successful product development and avoids shelving of drug substances prematurely. With this in mind, ExxPharma has established a drug delivery platform consisting of complimentary solubility enhancement technologies that handle drug substances irrespective of their physicochemical properties.
What do you see as the major industry critical issues over the next five years in regards to drug delivery?
Ali: As the industry continues to focus on continuous manufacturing to streamline processing and development time to bring a drug to market, the demand for quality excipients with defined attributes and reduced inline routine testing will rise. This will result in closer partnerships between excipient users and manufacturers. Of equal importance is the development of drugs using 3D printing which is gaining momentum as drug manufacturers’ focus on developing personalized medicines that target a patient’s specific dose and compliance requirements. Polymers for thermal processing and printing with pharmacopeial compliance will increase in demand. The excipient manufactures are working to develop the novel polymers to meet the 3D printing requirements for development of fast dissolving or controlled release oral dose tablets by fused deposition model (FDM), selective laser sintering (SLS) among other technologies. Thus, with the advent of personalized medicines by 3D printing, excipients such as Kollidon® 25, 30, 90F, Kollidon® VA64 and Kollidon® SR, Soluplus®, Kollisolv® PEG8000, Kollicoat® IR and Protect among others, will have an important role to play in the design of modern medicines with immediate and controlled release profiles.
Savla: How successful will innovative technologies such as 3D printing, nanotechnology, supercritical fluid be? Will they be able to reach commercial scales, be applicable to multiple products, prove economical, and provide significant advantages over established drug delivery technologies?
Despite knowing the challenges and issues of developing and bringing a poorly soluble drug to market, many companies continue to ignore spending time to implement drug delivery technologies. We need to quantitatively demonstrate the value of drug delivery to ensuring success of a drug product.
Patients are becoming more involved in their healthcare decisions. There will be a continued increase in the number of patients advocating for patient-friendly drug product. This will have a profound effect for geriatric patients. Drug developers will need to be fully aware of and address dosage form concerns of the elderly such as swallowability.
Dobry: We must continue to advance the formulation technology landscape to meet the needs of molecules that require delivery. We must also change the paradigms of our processing technology and supply chain infrastructure to develop manufacturing models of the future for the next generation of products. For example, patient-centric treatments are increasingly comprised of high-value/low-volume products and require not only enabling drug delivery technologies and appropriately scaled manufacturing but also an evolution of relationships with CDMOs to ensure that accelerated timelines can be achieved. As medicinal innovations such as live cell and gene therapies begin to come to patients, drug delivery will need to rise to the challenge of finding the best technologies to create drug products that can be effective. Lastly, the increase in personalized healthcare will require creative technological solutions that utilize new processes, devices and medicines.
Bauer: I like to think of it more in a positive way: in the future, many opportunities will open up for drug delivery approaches. Of course, on the one hand, some challenges will intensify, such as the need for novel functionalities that cannot be achieved with current compendial raw materials. It is clearly the supplier’s responsibility to develop new and innovative excipients – including novel excipients. At the same time, this endeavor needs to be supported by regulatory authorities like the U.S. FDA does. However, in the end we will all be successful only if pharmaceutical companies are willing to go first and no longer restrict themselves to be “the first second” when it comes to use and approval of novel chemistries in the excipient field. On the other hand, there are new technology developments, such as additive manufacturing. This has the potential to disrupt the pharmaceutical market as we know it today, driving towards decentralized manufacturing and changing established processes.
Taken together, if we succeed in combining new technologies and novel excipient approaches we are destined to making things possible that are hardly imaginable today.
Terefe: As the search for drug molecules that address unmet medical needs is continuing, pharmaceutical and biopharmaceutical companies are increasingly dealing with more complex small and large molecules that pose difficult drug delivery and manufacturing issues. The demand for the development of drug delivery systems that accurately deliver drugs to targeted body sites is very high.
Pediatric patients differ in their developmental status and dosing requirements from adults. Geriatric patients have compromised pharmacokinetics affected by co-morbidity, reduced organ function and multiple drug use. Hence most conventional drug delivery systems are not acceptable for these demographic groups. Hence, Development of age-appropriate pediatric and geriatric patients-focused versatile drug delivery systems is an area that requires attention. Increased research effort is required to develop appropriate delivery systems that effectively can handle new drugs and currently approved products.
In abuse deterrence, the technologies that have been developed so far are able, to some extent, reduce drug abuse by rendering dosage forms difficult to tamper with (such as grinding, extraction etc.). Drug abuse involving multiple pill ingestion, the most common form of abuse and is a cause of high mortality due to overdose, has not been effectively addressed to-date despite continued efforts.