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Drug Delivery and Translational Research Feb 2023Long-acting injectables (LAIs) have made a tremendous impact on clinical medicine. As evidence, dozens of approved LAI products are on the market. These LAI successes,...
Long-acting injectables (LAIs) have made a tremendous impact on clinical medicine. As evidence, dozens of approved LAI products are on the market. These LAI successes, in a large part, came from the clever chemistry of their materials that control drug delivery performance. Beyond their materials, what innovations and technologies led to LAI success? What were the scientific progressions and who were the people and their stories behind LAI success? The answers to these questions are interesting to hear about, learn from, and be inspired by. Many people from many diverse fields contributed to the scientific advancement, product development, and product launches of long-acting injectables. Over 50 years ago, LAI pioneers envisioned a host of new drug delivery concepts and engaged their enthusiasm to reduce their concepts to practice. In doing so, they considered a variety of materials, dosage forms, routes of administration, and manufacturing processes, and they had to devise new tools to support product development. Because of the wide technology breadth of long-acting injectables, this publication focuses on bioabsorbable LAIs formulated with polymeric excipients such as lactide/glycolide functional excipients. Their historical progression of polymer chemistry and formulation development is shared. Successes are highlighted with some backstories.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Absorbable Implants; Excipients; Delayed-Action Preparations
PubMed: 35989401
DOI: 10.1007/s13346-022-01199-2 -
Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
Advanced Drug Delivery Reviews May 2021Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused... (Comparative Study)
Comparative Study Review
Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be coupled with FDM 3D printing as a continuous manufacturing process. However, the crucial pharmaceutical polymers, formulation and process parameters must be investigated to establish HME-coupled FDM 3D printing. These advancements will lead the way towards developing continuous drug delivery systems for personalized therapy. This brief overview classifies pharmaceutical additive manufacturing, Hot Melt Extrusion, and Fused Deposition Modeling 3D printing techniques with a focus on coupling HME and FDM 3D printing processes. It also provides insights on the critical material properties, process and equipment parameters and limitations of successful HME-coupled FDM systems.
Topics: Drug Delivery Systems; Equipment Design; Excipients; Hot Melt Extrusion Technology; Humans; Pharmaceutical Preparations; Polymers; Printing, Three-Dimensional; Technology, Pharmaceutical
PubMed: 33571550
DOI: 10.1016/j.addr.2021.02.006 -
The Journal of Dermatological Treatment Mar 2022A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its... (Review)
Review
A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition.
Topics: Dermatitis, Atopic; Eczema; Emollients; Excipients; Humans; Skin; Treatment Outcome
PubMed: 32654550
DOI: 10.1080/09546634.2020.1789050 -
Immunology and Allergy Clinics of North... May 2022Excipients are the inactive ingredients in a drug or product that help to stabilize, preserve, or enhance the pharmacokinetics and bioavailability of the active... (Review)
Review
Excipients are the inactive ingredients in a drug or product that help to stabilize, preserve, or enhance the pharmacokinetics and bioavailability of the active ingredients. Excipient allergy is rare and hence often missed or misdiagnosed due to lack of awareness of the need to carefully review all drug ingredients. For the patient, excipient allergy can be frightening and potentially disruptive to health care delivery. This narrative review provides a clinically oriented, international, collaborative perspective on excipient allergy testing, management of future health care safety, limitations in our testing modalities, and barriers to optimal care.
Topics: Anaphylaxis; Excipients; Humans; Pharmaceutical Preparations
PubMed: 35469617
DOI: 10.1016/j.iac.2021.12.008 -
Journal of Pharmaceutical Sciences Jun 2021Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual...
Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics.
Topics: Excipients; Micelles; Polysorbates; Preservatives, Pharmaceutical; Surface-Active Agents
PubMed: 33387597
DOI: 10.1016/j.xphs.2020.12.030 -
Frontiers in Immunology 2022Nanotechnology carriers have become common in pharmaceutical products because of their benefits to drug delivery, including reduced toxicities and improved efficacy of... (Review)
Review
Nanotechnology carriers have become common in pharmaceutical products because of their benefits to drug delivery, including reduced toxicities and improved efficacy of active pharmaceutical ingredients due to targeted delivery, prolonged circulation time, and controlled payload release. While available examples of reduced drug toxicity through formulation using a nanocarrier are encouraging, current data also demonstrate that nanoparticles may change a drug's biodistribution and alter its toxicity profile. Moreover, individual components of nanoparticles and excipients commonly used in formulations are often not immunologically inert and contribute to the overall immune responses to nanotechnology-formulated products. Said immune responses may be beneficial or adverse depending on the indication, dose, dose regimen, and route of administration. Therefore, comprehensive toxicology studies are of paramount importance even when previously known drugs, components, and excipients are used in nanoformulations. Recent data also suggest that, despite decades of research directed at hiding nanocarriers from the immune recognition, the immune system's inherent property of clearing particulate materials can be leveraged to improve the therapeutic efficacy of drugs formulated using nanoparticles. Herein, I review current knowledge about nanoparticles' interaction with the immune system and how these interactions contribute to nanotechnology-formulated drug products' safety and efficacy through the lens of over a decade of nanoparticle characterization at the Nanotechnology Characterization Laboratory.
Topics: Tissue Distribution; Excipients; Nanotechnology; Nanostructures; Drug Delivery Systems; Pharmaceutical Preparations
PubMed: 36304452
DOI: 10.3389/fimmu.2022.984252 -
European Journal of Pharmaceutical... Mar 2024Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy... (Review)
Review
Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy with favorable pharmacokinetics and patient centricity. On the other hand, the above advantages are served by high and well reproducible quality attributes of the medicinal product where even flexible design and controlled processability offer success as well as possible longer product life-cycle for the manufacturers. Moreover, the specific demands of patients can be taken into account, including simplified dosing regimens, flexible dosage, drug combinations, palatability, and ease of swallowing. In the more than 70 years since the first modified-release formulation appeared on the market, many new formulations have been marketed and many publications have appeared in the literature. More unique and newer pharmaceutical technologies and excipients have become available for producing tailor-made particles with micrometer dimensions and beyond. All these have contributed to the fact that the sub-units (e.g. minitablets, pellets, microspheres) that make up a multiparticulate system can vary widely in composition and properties. Some units have mucoadhesive properties and others can float to contribute to a suitable release profile that can be designed for the multiparticulate formula as a whole. Nowadays, there are some available formulations on the market, which are able to release the active substance even for several months (3 or 6 months depending on the type of treatment). In this review, the latest developments in technologies that have been used for a long time are presented, as well as innovative solutions such as the applicability of 3D printing to produce subunits of multiparticulate systems. Furthermore, the diversity of multiparticulate systems, different routes of administration are also presented, touching the ones which are capable of carrying the active substance as well as the relevant, commercially available multiparticle-based medical devices. The versatility in size from 1 µm and multiplicity of formulation technologies promise a solid foundation for the future applications of dosage form design and development.
Topics: Humans; Drug Delivery Systems; Pharmaceutical Preparations; Excipients
PubMed: 38228279
DOI: 10.1016/j.ejps.2024.106704 -
International Journal of Molecular... Mar 2023Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1-1000 µm) are widely used as drug... (Review)
Review
Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1-1000 µm) are widely used as drug delivery systems, because they offer higher therapeutic and diagnostic performance compared to conventional drug delivery forms. These systems can be manufactured with many raw materials, especially polymers, most of which have been effective in improving the physicochemical properties and biological activities of active compounds. This review will focus on the in vivo and in vitro application in the last decade (2012 to 2022) of different active pharmaceutical ingredients microencapsulated in polymeric or lipid matrices, the main formulation factors (excipients and techniques) and mostly their biological activities, with the aim of introducing and discussing the potential applicability of microparticulate systems in the pharmaceutical field.
Topics: Drug Compounding; Drug Delivery Systems; Polymers; Excipients; Capsules; Microspheres; Particle Size
PubMed: 36982517
DOI: 10.3390/ijms24065441 -
International Journal of Pharmaceutics Oct 2020A handful of singular structures and laws can be observed in nature. They are not always evident but, once discovered, it seems obvious how to take advantage of them. In... (Review)
Review
A handful of singular structures and laws can be observed in nature. They are not always evident but, once discovered, it seems obvious how to take advantage of them. In chemistry, the discovery of reproducible patterns stimulates the imagination to develop new functional materials and technological or medical applications. Two clear examples are helical structures at different levels in biological polymers as well as ring and spherical structures of different size and composition. Rings are intuitively observed as holes able to thread elongated structures. A large number of real and fictional stories have rings as inanimate protagonists. The design, development or just discovering of a special ring has often been taken as a symbol of power or success. Several examples are the Piscatory Ring wore by the Pope of the Catholic Church, the NBA Championship ring and the One Ring created by the Dark Lord Sauron in the epic story The Lord of the Rings. In this work, we reveal the power of another extremely powerful kind of rings to fight against the pandemic which is currently affecting the whole world. These rings are as small as ~1 nm of diameter and so versatile that they are able to participate in the attack of viruses, and specifically SARS-CoV-2, in a large range of different ways. This includes the encapsulation and transport of specific drugs, as adjuvants to stabilize proteins, vaccines or other molecules involved in the infection, as cholesterol trappers to destabilize the virus envelope, as carriers for RNA therapies, as direct antiviral drugs and even to rescue blood coagulation upon heparin treatment. "One ring to rule them all. One ring to find them. One ring to bring them all and in the darkness bind them." J. R. R. Tolkien.
Topics: Betacoronavirus; Blood Coagulation; COVID-19; Coronavirus Infections; Cyclodextrins; Drug Carriers; Drug Stability; Excipients; Nanostructures; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Vaccines
PubMed: 32717282
DOI: 10.1016/j.ijpharm.2020.119689