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Wiley Interdisciplinary Reviews.... 2014The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements... (Review)
Review
The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements (CPCs), have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable CPCs, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and noncytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures.
Topics: Biocompatible Materials; Dosage Forms; Humans; Hydrogels; Injections; Nanostructures; Regenerative Medicine
PubMed: 24127230
DOI: 10.1002/wnan.1248 -
Molecular Pharmaceutics Oct 2010Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic... (Review)
Review
Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro-in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance.
Topics: Administration, Oral; Biological Availability; Body Fluids; Chemistry, Pharmaceutical; Dosage Forms; Drug Delivery Systems; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Solubility
PubMed: 20822152
DOI: 10.1021/mp100149j -
The AAPS Journal Sep 2012Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the... (Review)
Review
Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active Pharmaceutical Ingredients (API) and dosage forms. As in silico and in vitro tools become more sophisticated and our knowledge of physiological processes has grown, model simulations can provide a valuable confluence, tying-in in vitro data with in vivo data while offering mechanistic insights into clinical performance. To a formulation scientist, this unveils not just the parameters that are predicted to significantly impact dissolution/absorption, but helps probe explanations around drug product performance and address specific in vivo mechanisms. In formulation, development, in silico dissolution-absorption modeling can be effectively used to guide: API selection (form comparison and particle size properties), influence clinical study design, assess dosage form performance, guide strategy for dosage form design, and breakdown clinically relevant conditions on dosage form performance (pH effect for patients on pH-elevating treatments, and food effect). This minireview describes examples of these applications in guiding product development including those with strategies to mitigate observed clinical exposure liability or mechanistically probe product in vivo performance attributes.
Topics: Administration, Oral; Dosage Forms; Humans; Hydrogen-Ion Concentration; Models, Theoretical; Solubility; Therapeutic Equivalency
PubMed: 22644702
DOI: 10.1208/s12248-012-9372-3 -
Journal of Pharmacy & Pharmaceutical... 2019Particle engineering has become a hot topic in the field of modified-release delivery systems during last decades. It has a wide range of pharmaceutical applications and... (Review)
Review
Particle engineering has become a hot topic in the field of modified-release delivery systems during last decades. It has a wide range of pharmaceutical applications and is a bridge linking between drugs and drug delivery systems. Particles are an important part of many dosage forms and viewed as a carrier of drugs. Their size, shape, crystalline form, and structure directly affect the stability and releasing pattern of drugs. Engineering size or modifying particles by forming porous, core-shell, or skeleton structures can realize the development and utilization of functionally modified release systems (including fast-release systems, sustained-release systems, and targeted-release systems). However, there are certain problems in the practical application, such as bitter taste and coating damage. Combining with some polymer or lipid materials to form core-shell or embedded structures is considered as the key to taste masking. And, using cushioning agents is proven to be effective in preserving the integrity of the functional coating film of multiparticulates during tableting. To sum up, this review, from a particle engineering point, expounds the influence of different factors on the functionality of particles and offers some useful comments and suggestions for industry personnel.
Topics: Biological Availability; Drug Delivery Systems; Particle Size; Pharmaceutic Aids; Tablets; Technology, Pharmaceutical
PubMed: 31026393
DOI: 10.18433/jpps30253 -
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 -
Journal of Enzyme Inhibition and... Dec 2019Oral colon administration system has become a new method to treat intestinal diseases. The implementation of colon drug delivery system is restricted by many aspects,... (Review)
Review
Oral colon administration system has become a new method to treat intestinal diseases. The implementation of colon drug delivery system is restricted by many aspects, including physical and chemical properties, drug delivery mode, gastrointestinal physiological factors, and so on. Delivery methods to overcome these challenges revolve around the mechanisms of drug delivery, including the use of rational dosage forms to avoid the complex pH environment, and the prevention of drug release and absorption in the upper digestive tract.
Topics: Administration, Oral; Animals; Colon; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Liberation; Gastrointestinal Microbiome; Humans; Hydrogen-Ion Concentration; Intestinal Diseases; Polymers
PubMed: 31581863
DOI: 10.1080/14756366.2019.1655406 -
Drug Development and Industrial Pharmacy Dec 2017Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both...
Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.
Topics: Desiccation; Dosage Forms; Excipients; Powders; Technology, Pharmaceutical
PubMed: 28707494
DOI: 10.1080/03639045.2017.1355923 -
International Journal of Pharmaceutics Sep 2022Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D... (Review)
Review
Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.
Topics: Dosage Forms; Drug Liberation; Polymers; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical
PubMed: 35926751
DOI: 10.1016/j.ijpharm.2022.122066 -
Journal of Pharmacy & Pharmaceutical... 2006The pharmacist, both in community and hospital pharmacy practice, is often challenged with the preparation of a liquid dosage form not available commercially for... (Review)
Review
The pharmacist, both in community and hospital pharmacy practice, is often challenged with the preparation of a liquid dosage form not available commercially for paediatric patients, those adults unable to swallow tablets or capsules and patients who must receive medications via nasogastric or gastrostomy tubes. Recognising the lack of information available to healthcare professionals, a general discussion of the various parameters that may be modified in preparing these dosage forms and a tabulated summary of the dosage forms presented in the literature is described, which, although not exhaustive, will provide information on the formulation and stability of the most commonly prepared extemporaneous liquid dosage forms. An extensive survey of the literature and investigation of 83 liquid dosage forms revealed that stability considerations were of concern for only 7.2% of these liquid dosage forms, extemporaneously prepared from the following commercially available products: captopril, hydralazine hydrochloride, isoniazid, levothyroxine sodium, phenoxybenzamine hydrochloride and tetracycline hydrochloride. Inclusion of the antioxidant, sodium ascorbate in the liquid dosage form for captopril resulted in improved stability at 4 degrees C. Hydralazine hydrochloride, isoniazid and phenoxybenzamine hydrochloride were adversely affected due to interactions with excipients in the formulation, while the effect of the preservative in lowering the pH in a levothyroxine sodium mixture resulted in decreased stability. Interestingly, the instability in these formulations is primarily due to interactions between the drug substance and the excipients rather than degradation of the active pharmaceutical ingredient by standard routes such as oxidation, hydrolysis, photolysis or thermolysis. This low percentage however illustrates the low risk associated with these dosage forms investigated. It may be concluded that when considering the safety and efficacy of liquid dosage forms prepared extemporaneously, it is thus important to consider not only the stability of the drug substance but the entire formulation.
Topics: Dosage Forms; Drug Compounding; Drug Stability; Humans; Pharmaceutical Solutions; Pharmacists
PubMed: 17207422
DOI: No ID Found -
Journal of Controlled Release :... Dec 2015In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response of... (Review)
Review
In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response of drug products. Since the U.S. Food and Drug Administration (FDA) published a regulatory guidance on the development, evaluation, and applications of IVIVC for extended release (ER) oral dosage forms in 1997, IVIVC has been one of the most important issues in the field of pharmaceutics. However, even with the aid of the FDA IVIVC Guidance, only very limited Abbreviated New Drug Application (ANDA) submission for ER oral drug products included adequate IVIVC data to enable the completion of bioequivalence (BE) review within first review cycle. Establishing an IVIVC for non-oral dosage forms has remained extremely challenging due to their complex nature and the lack of in vitro release methods that are capable of mimicking in vivo drug release conditions. This review presents a general overview of recent advances in the development of IVIVC for complex non-oral dosage forms (such as parenteral polymeric microspheres/implants, and transdermal formulations), and briefly summarizes the knowledge gained over the past two decades. Lastly this review discusses possible directions for future development of IVIVC for complex non-oral dosage forms.
Topics: Animals; Delayed-Action Preparations; Dosage Forms; Drug Administration Routes; Humans; In Vitro Techniques; Pharmaceutical Preparations
PubMed: 26419305
DOI: 10.1016/j.jconrel.2015.09.052