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International Journal of Pharmaceutics Jul 2022Given the benefits of high printing precision and capability, the selective laser sintering technique has been used to manufacture medicines and implants with unique...
Given the benefits of high printing precision and capability, the selective laser sintering technique has been used to manufacture medicines and implants with unique engineering and functional properties. Using homogenized beams with a reduced thermal gradient and a larger diameter as an alternative energy source, the thermal stability and production efficiency of powder bed fusion would be improved. Herein, a novel homogenized spot melting (HSM) technology for pharmaceutical preparation was developed in this study. The melting behavior of typical pharmaceutical polymers under a homogenized spot was determined. A crystalline polymer with a low melting point was used as a solid binder, and the HSM printability and formation of drug-loaded formulations were explored. Oral solid dosage forms with different morphological and dissolution designs were prepared and evaluated under optimal formulation and process conditions. It was observed that HSM reduced the surface temperature distribution of the powder bed and improved the printability of drugs and excipients. Crystalline PEG 8000 with suitable flowability and heat conduction efficiency in the molten state was preferable for HSM printing. Incorporating 40% PEG 8000 as a solid binder was an effective strategy for HSM processing of unfused or unstable powders. Solid preparations with different structures and dissolution behaviors were successfully printed, suggesting that HSM is a promisingtechnique for personalized medicine.
Topics: Dosage Forms; Drug Liberation; Excipients; Polymers; Powders; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical
PubMed: 35718250
DOI: 10.1016/j.ijpharm.2022.121928 -
International Journal of Pharmaceutics May 2020Although solid dispersions have been reported as an efficient drug delivery system, the design of specific dosage forms for pharmaceutical therapy is necessary to... (Review)
Review
Although solid dispersions have been reported as an efficient drug delivery system, the design of specific dosage forms for pharmaceutical therapy is necessary to improve the solubility and bioavailability of poorly water-soluble drugs. Solid dispersions can be incorporated in general solid dosage forms such as powders, granules, capsules and tablets, but only to enhance solubility and the dissolution rate. However, further development of solid dispersions will be required in certain circumstances for further in vivo drug improvement of those solid dosage forms. In the current review, specific designs of solid dosage forms for controlled drug release will be reported. Moreover, methods and strategies for incorporating these solid dispersions into controlled drug release forms will also be discussed. Overall, the outlook of current studies will provide potential approaches for the further improvement of solid dispersions, especially for clinical developments in pharmaceutical therapy.
Topics: Biological Availability; Crystallization; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Design; Drug Liberation; Excipients; Solubility; Tablets
PubMed: 32234566
DOI: 10.1016/j.ijpharm.2020.119274 -
European Journal of Pharmaceutics and... Jan 1999
Topics: Drug Implants; Polymers; Tablets, Enteric-Coated
PubMed: 10234521
DOI: 10.1016/s0939-6411(98)00092-7 -
Professional Nurse (London, England) Feb 1993The oral route of drug administration is the most convenient for patients, with tablets emerging as the most popular solid oral dosage form used today. Standard...
The oral route of drug administration is the most convenient for patients, with tablets emerging as the most popular solid oral dosage form used today. Standard compressed, controlled-release and coated tablets are the most common form of solid oral dosages. A wide range and diversity of ingredients are often included in tablet formulations. A knowledge of the difference between tablet and capsule formulations should enable nurses to improve patient compliance with respect to solid oral dosage forms.
Topics: Administration, Oral; Delayed-Action Preparations; Dosage Forms; Humans; Tablets; Tablets, Enteric-Coated
PubMed: 8451252
DOI: No ID Found -
Journal of Controlled Release :... Sep 2023Classic methods for evaluating the disintegration and dissolution kinetics of solid dosage forms are no longer sufficient to meet the growing demands in the... (Review)
Review
Classic methods for evaluating the disintegration and dissolution kinetics of solid dosage forms are no longer sufficient to meet the growing demands in the pharmaceutical field. Hence, scientists have turned to imaging techniques and computer technology to develop innovative visualization methods. These methods allow for a visual understanding of the disintegration or dissolution process and offer valuable insights into the drug release kinetics. This article aims to provide an overview of the commonly used imaging techniques and their applications in studying the disintegration or dissolution of solid dosage forms. Therefore, imaging presents a novel and alternative approach to understanding the mechanisms of disintegration and dissolution in the formulation study of solid dosages.
Topics: Chemistry, Pharmaceutical; Tablets; Solubility; Drug Liberation; Kinetics; Dosage Forms
PubMed: 37567508
DOI: 10.1016/j.jconrel.2023.08.013 -
Drug Discovery Today Jul 2008Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low... (Review)
Review
Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. Self-emulsifying drug delivery systems (SEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Conventional SEDDS, however, are mostly prepared in a liquid form, which can produce some disadvantages. Accordingly, solid SEDDS (S-SEDDS), prepared by solidification of liquid/semisolid self-emulsifying (SE) ingredients into powders, have gained popularity. This article gives an overview of the recent advances in the study of S-SEDDS, especially the related solidification techniques and the development of solid SE dosage forms. Finally, the existing problems and the possible future research directions in this field are pointed out.
Topics: Animals; Biopharmaceutics; Chemistry, Pharmaceutical; Dosage Forms; Drug Delivery Systems; Emulsions; Humans
PubMed: 18598917
DOI: 10.1016/j.drudis.2008.04.006 -
Drug Development and Industrial Pharmacy Aug 2016Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is... (Review)
Review
CONTEXT
Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model.
OBJECTIVE
The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms.
METHODS
Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described.
RESULTS
There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of "from powder to tablet" is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible.
CONCLUSION
A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Dosage Forms; Drug Industry; Powders; Tablets; Technology, Pharmaceutical
PubMed: 26592545
DOI: 10.3109/03639045.2015.1122607 -
Materials Science & Engineering. C,... Mar 2018At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate...
At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers.
Topics: Acetaminophen; Capsules; Drug Carriers; Drug Liberation; Microscopy, Electron, Scanning; Polyethylene Glycols; Printing, Three-Dimensional; Tablets
PubMed: 29519432
DOI: 10.1016/j.msec.2017.07.003 -
European Journal of Pharmaceutical... Aug 2022On demand production of totally customizable combinative preparations is a central goal of a patient-centric pharmaceutical supply chain. Additive manufacturing...
On demand production of totally customizable combinative preparations is a central goal of a patient-centric pharmaceutical supply chain. Additive manufacturing techniques like fused deposition modeling (FDM) could be key technologies towards such individualized dosage forms. As so far only a limited number of studies on 3D printed combinative preparations applying FDM have been reported, a core-shell dosage form was the focus of the present study. Dosage forms with an initial and a sustained release part with theophylline as model API were successfully produced applying a dual nozzle FDM 3D printer. Investigations identified microstructural defects at the interface between the two formulations by means of µCT analysis. Dissolution testing proved the achievement of the intended release profile. In combination with additionally characterized release profile of single material prints of different shapes, the combinative release profiles could be predicted by developing model equations and taking into account the geometric composition. As these model approaches can accordingly facilitate the prediction of API release from 3D printed combinative preparations with only data from single material release. This is a first step towards a truly individualized and reliable patient-centric pharmaceutical supply via 3D printing.
Topics: Dosage Forms; Drug Compounding; Drug Liberation; Humans; Kinetics; Pharmaceutical Preparations; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical
PubMed: 35662635
DOI: 10.1016/j.ejps.2022.106221 -
European Journal of Pharmaceutical... Aug 2023There is a growing interest in enhancing the acceptability of paediatric pharmaceutical formulations. Solid oral dosage forms (SODF), especially multiparticulates, are...
There is a growing interest in enhancing the acceptability of paediatric pharmaceutical formulations. Solid oral dosage forms (SODF), especially multiparticulates, are being considered as an alternative to liquid formulations, but they may compromise palatability when large volumes are required for dosing. We hypothesised that a binary mixture of multiparticulates for paediatric use, designed to increase the formulation maximum packing fraction, could reduce the viscosity of the mixture in soft food and facilitate swallowing. Using the Paediatric Soft Robotic Tongue (PSRT) - an in vitro device inspired by the anatomy and physiology of 2-year-old children - we investigated the oral phase of swallowing for multi-particulate formulations, i.e., pellets (350 and 700 µm particles), minitablets (MTs, 1.8 mm), and their binary mixtures (BM), by evaluating oral swallowing time, the percentage of particles swallowed, and post-swallow residues. We also conducted a systematic analysis of the effect of the administration method, bolus volume, carrier type, particle size, and particle volume fraction on pellets swallowability. The results demonstrated that the introduction of pellets affected the flowing ability of the carriers, increasing shear viscosity. The size of the pellets did not appear to influence particle swallowability but raising the particle volume fraction (v.f.) above 10% resulted in a decrease in the percentage of particles swallowed. At v.f. 0.4, pellets were easier to swallow (+ 13.1%) than MTs, being the administration method used highly dependent on the characteristics of the multi-particulate formulation under consideration. Finally, mixing MTs with only 24% of pellets improved particle swallowability, achieving swallowing levels similar to those of pellets alone. Thus, combining SODF, i.e., MTs and pellets, improves MT swallowability, and offers new possibilities for adjusting product palatability, being particularly attractive for combination products.
Topics: Child; Humans; Child, Preschool; Tablets; Administration, Oral; Deglutition; Drug Implants; Viscosity; Dosage Forms
PubMed: 37210000
DOI: 10.1016/j.ejps.2023.106471