Search Results (13)

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

Background/Objectives: Quality by Design (QbD) has revolutionized pharmaceutical development by transitioning from reactive quality testing to proactive, science-driven methodologies. Rooted in ICH Q8–Q11 guidelines, QbD emphasizes defining Critical Quality Attributes (CQAs), establishing design spaces, and integrating risk management to enhance product robustness and regulatory flexibility. This review critically examines QbD’s theoretical frameworks, implementation workflows, and industrial applications, aiming to bridge academic research and commercial practices while addressing emerging challenges in biologics, advanced therapies, and personalized medicine. Methods: The review synthesizes regulatory guidelines, case studies, and multidisciplinary tools, including Design of Experiments (DoE), Failure Mode Effects Analysis (FMEA), Process Analytical Technology (PAT), and multivariate modeling. It evaluates QbD workflows—from Quality Target Product Profile (QTPP) definition to control strategies—and explores advanced technologies like AI-driven predictive modeling, digital twins, and continuous manufacturing. Results: QbD implementation reduces batch failures by 40%, optimizes dissolution profiles, and enhances process robustness through real-time monitoring (PAT) and adaptive control. However, technical barriers, such as nonlinear parameter interactions in complex systems, and regulatory disparities between agencies hinder broader adoption. Conclusions: QbD significantly advances pharmaceutical quality and efficiency, yet requires harmonized regulatory standards, lifecycle validation protocols, and cultural shifts toward interdisciplinary collaboration. Emerging trends, including AI-integrated design space exploration and 3D-printed personalized medicines, promise to address scalability and patient-centric needs. By fostering innovation and compliance, QbD remains pivotal in achieving sustainable, patient-focused drug development. Full article

Oral solid drug delivery continues to be the gold standard in pharmaceutical formulations, owing to its cost-effectiveness, ease of administration, and high patient compliance. Tablets, the most widely used dosage form, are favored for their precise dosing, simplicity, and economic advantages. Among these, controlled release (CR) tablets stand out for their ability to maintain consistent drug levels, enhance therapeutic efficacy, and reduce dosing frequency, thereby improving patient adherence and treatment outcomes. A well-designed CR system ensures a sustained and targeted drug supply, optimizing therapeutic performance while minimizing side effects. This review delves into the latest advancements in CR formulations, with a particular focus on hydrophilic matrix systems, which regulate drug release through mechanisms such as swelling, diffusion, and erosion. These systems rely on a variety of polymers as drug-retarding agents to achieve tailored release profiles. Recent breakthroughs in crystal engineering and polymer science have further enhanced drug solubility and bioavailability, addressing critical challenges associated with poorly soluble drugs. In terms of manufacturing, direct compression has emerged as the most efficient method for producing CR tablets, streamlining production while ensuring consistent drug release. The integration of the Quality by Design framework has been instrumental in optimizing product performance by systematically linking formulation and process variables to patient-centric quality attributes. The advent of cutting-edge technologies such as artificial intelligence and 3D printing is revolutionizing the field of CR formulations. AI enables predictive modeling and data-driven optimization of drug release profiles, while 3D printing facilitates the development of personalized medicines with highly customizable release kinetics. These innovations are paving the way for more precise and patient-specific therapies. However, challenges such as regulatory hurdles, patent constraints, and the need for robust in vivo validation remain significant barriers to the widespread adoption of these advanced technologies. This succinct review underscores the synergistic integration of traditional and emerging strategies in the development of CR matrix tablets. It highlights the potential of hydrophilic and co-crystal matrix systems, particularly those produced via direct compression, to enhance drug bioavailability, improve patient adherence, and deliver superior therapeutic outcomes. By bridging the gap between established practices and innovative approaches, this field is poised to address unmet clinical needs and advance the future of oral drug delivery. Full article

In recent years, with the increasing patient population, the need for complex and patient-centric medications has increased enormously. Traditional manufacturing techniques such as direct blending, high shear granulation, and dry granulation can be used to develop simple solid oral medications. However, it is well known that “one size fits all” is not true for pharmaceutical medicines. Depending on the age, sex, and disease state, each patient might need a different dose, combination of medicines, and drug release pattern from the medications. By employing traditional practices, developing patient-centric medications remains challenging and unaddressed. Over the last few years, much research has been conducted exploring various additive manufacturing techniques for developing on-demand, complex, and patient-centric medications. Among all the techniques, nozzle-based additive manufacturing platforms such as pressure-assisted microsyringe (PAM) and fused deposition modeling (FDM) have been investigated thoroughly to develop various medications. Both nozzle-based techniques involve the application of thermal energy. However, PAM can also be operated under ambient conditions to process semi-solid materials. Nozzle-based techniques can also be paired with the hot melt extrusion (HME) process for establishing a continuous manufacturing platform by employing various in-line process analytical technology (PAT) tools for monitoring critical process parameters (CPPs) and critical material attributes (CMAs) for delivering safe, efficacious, and quality medications to the patient population without compromising critical quality attributes (CQAs). This review covers an in-depth discussion of various critical parameters and their influence on product quality, along with a note on the continuous manufacturing process, quality by design, and future perspectives. Full article

Orodispersible films (ODFs) are thin, mechanically strong, and flexible polymeric films that are designed to dissolve or disintegrate rapidly in the oral cavity for local and/or systemic drug delivery. This review examines various aspects of ODFs and their potential as a drug delivery system. Recent advancements, including the detailed exploration of formulation components, such as polymers and plasticizers, are briefed. The review highlights the versatility of preparation methods, particularly the solvent-casting production process, and novel 3D printing techniques that bring inherent flexibility. Three-dimensional printing technology not only diversifies active compounds but also enables a multilayer approach, effectively segregating incompatible drugs. The integration of nanoparticles into ODF formulations marks a significant breakthrough, thus enhancing the efficiency of oral drug delivery and broadening the scope of the drugs amenable to this route. This review also sheds light on the diverse in vitro evaluation methods utilized to characterize ODFs, ongoing clinical trials, approved marketed products, and recent patents, providing a comprehensive outlook of the evolving landscape of orodispersible drug delivery. Current patient-centric approaches involve developing ODFs with patient-friendly attributes, such as improved taste masking, ease of administration, and enhanced patient compliance, along with the personalization of ODF formulations to meet individual patient needs. Investigating novel functional excipients with the potential to enhance the permeation of high-molecular-weight polar drugs, fragile proteins, and oligonucleotides is crucial for rapid progress in the advancing domain of orodispersible drug delivery. Full article

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and S_mix. To optimize the formulation, a Box–Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings. Full article

Immunotherapy with checkpoint inhibitors (CPIs) and cell-based products has revolutionized the treatment of various solid tumors and hematologic malignancies. These agents have shown unprecedented response rates and long-term benefits in various settings. These clinical advances have also pointed to the need for new or adapted approaches to trial design and assessment of efficacy and safety, both in the early and late phases of drug development. Some of the conventional statistical methods and endpoints used in other areas of oncology appear to be less appropriate in immuno-oncology. Conversely, other methods and endpoints have emerged as alternatives. In this article, we discuss issues related to trial design in the early and late phases of drug development in immuno-oncology, with a focus on CPIs. For early trials, we review the most salient issues related to dose escalation, use and limitations of tumor response and progression criteria for immunotherapy, the role of duration of response as an endpoint in and of itself, and the need to conduct randomized trials as early as possible in the development of new therapies. For late phases, we discuss the choice of primary endpoints for randomized trials, review the current status of surrogate endpoints, and discuss specific statistical issues related to immunotherapy, including non-proportional hazards in the assessment of time-to-event endpoints, alternatives to the Cox model in these settings, and the method of generalized pairwise comparisons, which can provide a patient-centric assessment of clinical benefit and be used to design randomized trials. Full article

Topical treatments are essential approaches to skin diseases but are associated with poor adherence. Topical vehicles have the primary purpose of ensuring drug effectiveness (by modulating drug stability and delivery, as well as skin properties) but have a marked impact on treatment outcomes as they influence patient satisfaction and, consequently, adherence to topical treatments. There is also a wide variety of vehicles available for topical formulations, which can complicate the decisions of clinicians regarding the most appropriate treatments for specific skin disorders. One of the possible strategies to improve topical-treatment adherence is the implementation of patient-centric drug-product design. In this process, the patient’s needs (e.g., those related to motor impairment), the needs associated with the disease (according to the skin lesions’ characteristics), and the patient’s preferences are taken into consideration and translated into a target product profile (TPP). Herein, an overview of topical vehicles and their properties is presented, along with a discussion of the patient-centric design of topical dermatological medicines and the proposal of TPPs for some of the most common skin diseases. Full article

Medication non-adherence poses considerable challenges in managing chronic diseases and is associated with almost 200,000 deaths and EUR 80–125 billion in potentially preventable direct (e.g., hospitalizations, waste of medication) and indirect (e.g., work productivity losses) costs in the European Union alone. The increasing awareness of the contribution of the acceptability of drug products by the patient to medication adherence and clinical outcomes is driving the integration of patient-centric drug product design (PCDPD) into the pharmaceutical development process. Regulatory agencies have addressed the relevancy of placing the patient at the center of pharmaceutical development. The EMA has issued guidelines/reflection papers for pediatric and older populations while the FDA has developed a series of guidance documents on patient focused drug development with the primary goal to better incorporate the patient’s voice in drug development and evaluation. PCDPD can be defined as the process of identifying the comprehensive needs of the target patient population to support the design of drug products. Three major factors are analyzed in PCDPD, namely, the patient, drug, and drug product characteristics. This systematic approach integrates this insight, which is translated to a target product profile (TPP) to drive the pharmaceutical product design process. Two case studies are presented focused on the pediatric population and on patients with a chronic skin disorder (psoriasis), which will highlight the roadmap for a successful PCDPD. Full article

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in-use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in-use stability protocols should be preferred in the stability evaluation of pediatric formulations. Full article

Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement. Full article

Oral drug administration provided as solid oral dosage forms (SODF) remains the major route of drug therapy in primary and secondary care. There is clear evidence for a growing number of clinically relevant swallowing issues (e.g., dysphagia) in the older patient population, especially when considering the multimorbid, frail, and polymedicated patients. Swallowing impairments have a negative impact on SODF administration, which leads to poor adherence and inappropriate alterations (e.g., crushing, splitting). Different strategies have been proposed over the years in order to enhance the swallowing experience with SODF, by using conventional administration techniques or applying swallowing aids and devices. Nevertheless, new formulation designs must be considered by implementing a patient centric approach in order to efficiently improve SODF administration by older patient populations. Together with appropriate SODF size reductions, innovative film coating materials that can be applied to SODF and provide swallowing safety and efficacy with little effort being required by the patients are still needed. With that in mind, a literature review was conducted in order to identify the availability of patient centric coating materials claiming to shorten esophageal transit times and improve the overall SODF swallowing experience for older patients. The majority of coating technologies were identified in patent applications, and they mainly included well-known water soluble polymers that are commonly applied into pharmaceutical coatings. Nevertheless, scientific evidence demonstrating the benefits of given SODF coating materials in the concerned patient populations are still very limited. Consequently, the availability for safe, effective, and clinically proven solutions to address the increasing prevalence of swallowing issues in the older patient population is still limited. Full article

Medication adherence is a growing concern for public health and poor adherence to therapy has been associated with poor health outcomes and higher costs for patients. Interventions for improving adherence need to consider the characteristics of the individual therapeutic regimens according to the needs of the patients. In particular, geriatric and paediatric populations as well as dermatological patients have special needs/preferences that should be considered when designing drug products. Patient Centric Drug Product Pharmaceutical Design (PCDPD) offers the opportunity to meet the needs and preferences of patients. Packaging, orodispersible formulations, fixed dose combinations products, multiparticulate formulations, topical formulations and 3D printing are of particular relevance in a PCDPD process. These will be addressed in this review as well as their impact on medication adherence. Full article