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Current Pharmaceutical Design 2015The pharmaceutical industry still produces the vast majority of their products, from powdered ingredients, in the form of solid doses. Despite their ubiquity, powders... (Review)
Review
The pharmaceutical industry still produces the vast majority of their products, from powdered ingredients, in the form of solid doses. Despite their ubiquity, powders are difficult materials to characterise and understand, as evidenced by the frequent problems encountered during manufacture. The reason for this is their complex rheological behaviour coupled with numerous environmental variations, such as humidity. Equally, the range of processes used to manipulate powders subject them to extremes of stress from high compaction loads seen in compactors to the dispersed state seen in fluidised bed dryers. Thus, it is evident that ensuring that the powders characteristics are compatible with the way they are to be processed is a clear prerequisite for today's Quality by Design driven manufacturing. Modern, computer controlled instrumental techniques, including the dynamic, bulk and shear property measurements have enabled direct measurements of a powders response to aeration, consolidation and flow rate - all at low stresses - as well as quantifying shear and bulk properties (such as density, compressibility and permeability). In order to demonstrate how fully characterising a powder can be used in the design, operation and troubleshooting of processes, this paper will present examples of common pharmaceutical unit operations and the different powder characteristics that most influence the performance of each.
Topics: Dosage Forms; Humans; Pharmaceutical Preparations; Powders; Technology, Pharmaceutical
PubMed: 26446474
DOI: 10.2174/1381612821666151008124159 -
Expert Opinion on Drug Delivery Dec 2018The development of oral sustained release dosage forms has been a longstanding goal due to the potential for ease of administration, improved pharmacokinetics, reduced... (Review)
Review
INTRODUCTION
The development of oral sustained release dosage forms has been a longstanding goal due to the potential for ease of administration, improved pharmacokinetics, reduced dosing frequency, and improved adherence. The benefits of multiday single-dose drug delivery are evident in the success and patient adoption of injected and implanted dosage forms. However, in the space of oral medications, all current commercially available gastric resident dosage forms, and most in development, are limited to gastric residence of less than 1 day.
AREAS COVERED
Reviews of systems to extend gastric residence reveal that 1 day or more residence has been an unmet challenge. New dosage forms are in development that seek to address many of the key physiological and design challenges of long-term gastric retention beyond 24 h and up to a week or longer. The present analysis highlights the design, material considerations and implications of unfolding dosage form systems with ultra-long-term gastric residence.
EXPERT OPINION
The development of oral dosage forms providing sustained release of high potency medications over days or weeks could transform care, significantly decrease patient burden in chronic disease management and improve outcomes.
Topics: Administration, Oral; Delayed-Action Preparations; Dosage Forms; Drug Delivery Systems; Humans; Stomach
PubMed: 30392404
DOI: 10.1080/17425247.2018.1544615 -
International Journal of Pharmaceutics May 2021A novel approach to solid dosage form design is investigated, whereby instead of blending the ingredients and subsequently compacting the mixture, the dosage form is...
A novel approach to solid dosage form design is investigated, whereby instead of blending the ingredients and subsequently compacting the mixture, the dosage form is made by assembling prefabricated components, each with a specific function. The approach was used to formulate a weak-base API (active pharmaceutical ingredient), such that the modular dosage forms exhibited pH-independent drug release. Tablet-like dosage forms of ciprofloxacin (CPR), used as model weak-base drug, were prepared in order to generate dosage forms exhibiting pH-independent drug release. The dosage forms were made by assembling two types of prefabricated modules onto 3D stacks. The modules were hydroxypropyl methylcellulose circular film wafers, loaded with either CPR or citric acid (CA). CA-wafers served the function of pH-modifier modules in the microenvironment of the dosage form during the dissolution process. In vitro drug release from dosage forms consisting of CA- and CPR-wafers stacked in alternate sequence was compared with the release from assemblies containing CPR-wafers only, under pH = 1.2 and pH = 6.8 conditions. In the absence of CA-wafers, CPR release was ~25-fold slower at pH = 6.8 compared to pH = 1.2. Inclusion of CA-wafers in the dosage form assembly accelerated and decelerated drug release at pH = 6.8 and pH = 1.2, respectively, which resulted in overlapping drug release profiles under the two pH conditions. The two drug release profiles met the criteria for sameness as assessed by the f (difference) and f (similarity) factors. Modeling of drug release kinetics pointed toward polymer erosion as the primary mechanism of drug release for the overlapping pH = 1.2 and pH = 6.8 profiles. In terms of their drug release properties, the multi-modular dosage form assemblies exhibited the attributes and behavior of single bodies, rather than the combined contributions from multiple individually-operating modules. The initial geometry of the dosage form, characterized by the surface area (SA), volume (V) and SA/V ratio accounted for drug release kinetics in the same fashion as for traditional tablet compacts.
Topics: Delayed-Action Preparations; Dosage Forms; Hydrogen-Ion Concentration; Hypromellose Derivatives; Solubility; Tablets
PubMed: 33775729
DOI: 10.1016/j.ijpharm.2021.120518 -
International Journal of Pharmaceutics Sep 2021In this work, the role of excipient molecular weight in drug release by close-packed, highly drug-loaded fibrous dosage forms is investigated. Three dosage forms with...
In this work, the role of excipient molecular weight in drug release by close-packed, highly drug-loaded fibrous dosage forms is investigated. Three dosage forms with 87 wt% ibuprofen drug, and 13 wt% hydroxypropyl methylcellulose (HPMC) excipient of molecular weights 10, 26, and 86 kg/mol were prepared by wet 3D-patterning and drying. Upon immersion in a dissolution fluid, the dosage form with 10 kg/mol excipient fragmented and dissolved within 10 minutes. The dosage form with 26 kg/mol excipient fragmented slower, and dissolved in 60 minutes. The dosage form with 86 kg/mol excipient, however, did not fragment at all. Instead, a thick, highly viscous mass was formed that eroded slowly, in 500 minutes. Theoretical models suggest that the dissolution fluid rapidly percolates the inter-fiber void space, and a capillary pressure develops in the pores of the fibers. The fluid then diffuses into the fiber walls, and they transition to a viscous suspension. If the molecular weight of the excipient is small (~10 kg/mol), the viscosity is low and the suspension fragments and dissolves rapidly. If the molecular weight is moderate (~30 kg/mol), the fragmentation and dissolution rates are slower. If the molecular weight is large (~100 kg/mol), a thick, highly viscous mass is formed from which drug release is very slow. Thus, by appropriate choice of the molecular weight of the excipient, a wide range of drug release rates by close-packed, highly drug-loaded fibrous dosage forms can be realized.
Topics: Dosage Forms; Drug Liberation; Excipients; Hypromellose Derivatives; Molecular Weight; Solubility; Tablets
PubMed: 33246051
DOI: 10.1016/j.ijpharm.2020.120009 -
Lancet (London, England) Feb 1980
Topics: Biological Availability; Delayed-Action Preparations; Pharmaceutical Preparations; Tablets
PubMed: 6101819
DOI: 10.1016/s0140-6736(80)90914-9 -
International Journal of Pharmaceutics Jan 2007The purpose of this article is to review USP and non-pharmacopeial dissolution testing methods for conventional and novel pharmaceutical dosage forms and give an insight... (Review)
Review
The purpose of this article is to review USP and non-pharmacopeial dissolution testing methods for conventional and novel pharmaceutical dosage forms and give an insight to possible alternatives in drug dissolution study design and appropriate choices for dissolution media. For each dosage form first the USP method(s) for dissolution testing are reviewed followed by alternative methods used in research and development.
Topics: Administration, Cutaneous; Aerosols; Capsules; Chemistry, Pharmaceutical; Dosage Forms; Excipients; Gelatin; Mouth; Powders; Solubility; Tablets
PubMed: 17084051
DOI: 10.1016/j.ijpharm.2006.10.001 -
International Journal of Pharmaceutics Mar 2023Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing in this study. The tablet...
Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing in this study. The tablet batches were prepared using either copovidone (N-vinyl-2-pyrrolidone and vinyl acetate, PVP/VA) or polyvinyl alcohol (PVA) and activated carbon (AC) as radiation absorbent, which was added to improve the sintering of the polymer. The physical properties of the dosage forms were evaluated at different pigment concentrations (i.e., 0.5 and 1.0 wt%) and at different laser energy inputs. The mass, hardness, and friability of the tablets were found to be tunable and structures with greater mass and mechanical strength were obtained with increasing carbon concentration and energy input. Amorphization of the active pharmaceutical ingredient in the drug-loaded batches, containing 10 wt% naproxen and 1 wt% AC, was achieved in-situ during printing. Thus, amorphous solid dispersions were prepared in a single-step process and produced tablets with mass losses below 1 wt%. These findings show how the properties of dosage forms can be tuned by careful selection of the process parameters and the powder formulation. SLS 3D printing can therefore be considered to be an interesting and promising technique for the fabrication of personalized medicines.
Topics: Powders; Drug Compounding; Tablets; Polymers; Lasers; Printing, Three-Dimensional; Drug Liberation; Technology, Pharmaceutical; Dosage Forms
PubMed: 36849041
DOI: 10.1016/j.ijpharm.2023.122780 -
Current Pharmaceutical Design 2015
Topics: Dosage Forms; Drug Delivery Systems; Humans; Nanoparticles; Pharmaceutical Preparations; Powders; Technology, Pharmaceutical
PubMed: 26459802
DOI: 10.2174/1389450116999151013124428 -
Expert Review of Vaccines Jul 2010
Topics: Dosage Forms; Humans; Vaccines
PubMed: 20624039
DOI: 10.1586/erv.10.73 -
Journal of Pharmaceutical Sciences Oct 2010It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low... (Review)
Review
It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.
Topics: Administration, Oral; Biological Availability; Capsules; Dosage Forms; Gelatin; Solubility
PubMed: 20737624
DOI: 10.1002/jps.22151