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Molecules (Basel, Switzerland) Jun 2023One of the major challenges in the development of effective pharmaceutical formulations for oral administration is the poor solubility of active pharmaceutical... (Review)
Review
One of the major challenges in the development of effective pharmaceutical formulations for oral administration is the poor solubility of active pharmaceutical ingredients. For this reason, the dissolution process and drug release from solid oral dosage forms, such as tablets, is usually thoroughly studied in order to understand the dissolution behaviour under various conditions and optimize the formulation accordingly. Standard dissolution tests used in the pharmaceutical industry provide information on the amount of drug released over time; however, these do not allow for a detailed analysis of the underlying chemical and physical mechanisms of tablet dissolution. FTIR spectroscopic imaging, by contrast, does offer the ability to study these processes with high spatial and chemical specificity. As such, the method allows us to see the chemical and physical processes which occur inside the tablet as it dissolves. In this review, the power of ATR-FTIR spectroscopic imaging is demonstrated by presenting a number of successful applications of this chemical imaging technique to dissolution and drug release studies for a range of different pharmaceutical formulations and study conditions. Understanding these processes is essential for the development of effective oral dosage forms and optimization of pharmaceutical formulations.
Topics: Drug Liberation; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets; Diagnostic Imaging
PubMed: 37375260
DOI: 10.3390/molecules28124705 -
Journal of Pharmacy & Pharmaceutical... 2018The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro... (Review)
Review
A Survey of the Regulatory Requirements for BCS-Based Biowaivers for Solid Oral Dosage Forms by Participating Regulators and Organisations of the International Generic Drug Regulators Programme.
PURPOSE
The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations.
METHODS
Differences and similarities regarding solubility, permeability, dissolution, excipients and fixed-dose combination products, were identified and compared in a detailed survey of each participant's criteria for BCS-based biowaivers. These criteria were determined based upon the participants' respective regulatory guidance documents, policies and practices.
RESULTS
This review has, with the exception of two participants who do not accept BCS-based biowaivers, revealed that most IGDRP participants interpret the BCS principles and conditions similarly but notable differences exist in the application of these principles. Conclusion: Although many similarities exist, this review identifies several opportunities for greater convergence of regulatory requirements amongst the surveyed jurisdictions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Administration, Oral; Biopharmaceutics; Dosage Forms; Humans; International Cooperation; Surveys and Questionnaires
PubMed: 29382433
DOI: 10.18433/J3X93K -
Yakugaku Zasshi : Journal of the... 2018Biopharmaceuticals are often formulated as liquid dosage forms. During manufacturing and storage, protein molecules and active pharmaceutical ingredients form aggregates... (Review)
Review
Biopharmaceuticals are often formulated as liquid dosage forms. During manufacturing and storage, protein molecules and active pharmaceutical ingredients form aggregates due to various stresses, including shaking and agitation, as well as by contact with silicone oils coated on pre-fillable syringes. The diameter of protein aggregates ranges from 15-20 nm, and that of dimers comprising a large number of antibody molecules can be up to 100 μm. Among these aggregates, those with a diameter of <100 nm are called nanometer aggregates, while those ranging between 100 nm and 1 μm are called sub-micron aggregates, and those ranging between 1 and 100 μm are called micron aggregates. In the last ten years, aggregates have been studied to determine their physical characteristics and their impact on immunogenicity. As a result, novel analytical methods and instruments for such characterizations have been established for a majority of aggregates, including those that are difficult to evaluate. Here, the biophysical features of protein aggregates are explained, followed by an introduction to the different methods for aggregate characterization, including their advantages and actual results. Finally, future perspectives and expectations regarding the characterization of protein aggregates are proposed.
Topics: Biological Products; Dosage Forms; Drug Contamination; Drug Stability; Nanoparticles; Particle Size; Protein Aggregates
PubMed: 30504664
DOI: 10.1248/yakushi.18-00020-4 -
Basic & Clinical Pharmacology &... Feb 2016Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor... (Review)
Review
Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring patient compliance. Nevertheless, cell-penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP-mediated transepithelial delivery of therapeutic peptides and proteins from the intestine. Two approaches may be pursued: co-administration of the carrier and therapeutic peptide in the form of complexes obtained by simple bulk mixing, or administration of covalent conjugates demanding more advanced production methodologies. These formulation approaches have their pros and cons, and which is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP-mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed to delay enzymatic degradation of the CPP. The mechanisms by which CPPs translocate across membranes are not fully understood, but possibly involve endocytosis as well as direct translocation, and the CPP-mediated transepithelial delivery of cargo drugs thus likely involves similar mechanisms for the initial membrane interaction and translocation. However, the mechanisms responsible for transcytosis of the cargo drug, if taken up by an endocytic mechanism, or direct translocation across the epithelium are so far not known.
Topics: Cell-Penetrating Peptides; Dosage Forms; Drug Administration Routes; Drug Delivery Systems; Humans
PubMed: 26525297
DOI: 10.1111/bcpt.12515 -
Pharmaceutical Research Mar 2022To develop a new direct granule fed 3D printing method for manufacturing pharmaceutical solid dosage forms with porous structures using a thermal droplet deposition...
PURPOSE
To develop a new direct granule fed 3D printing method for manufacturing pharmaceutical solid dosage forms with porous structures using a thermal droplet deposition technology.
METHODS
Eudragit® E PO was used as the model polymer, which is well-known to be not FDM printable without additives. Wet granulation was used to produce drug loaded granules as the feedstock. The flow and feedability of the granules were evaluated. The physicochemical properties and in vitro drug release performance of the granules and the printed tablets were fully characterised.
RESULTS
Using the method developed by this study, Eudragit E PO was printed with a model drug into tablets with infills ranging from 30-100%, without additives. The drug was confirmed to be molecularly dispersed in the printed tablets. The printing quality and performances of the porous tablets were confirmed to be highly compliant with the pharmacopeia requirement. The level of infill density of the porous tablets had a significant effect on their in vitro drug release performance.
CONCLUSION
This is the first report of thermal droplet deposition printing via direct granule feeding. The results of this study demonstrated that this new printing method can be used as a potentially valuable alternative for decentralised pharmaceutical solid dosage form manufacturing.
Topics: Dosage Forms; Drug Liberation; Porosity; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical
PubMed: 35194719
DOI: 10.1007/s11095-022-03198-x -
International Journal of Pharmaceutics Mar 2024Three-dimensional printing (3DP) is an emerging technology, offering the possibility for the development of dose-customized, effective, and safe solid oral dosage forms... (Review)
Review
Three-dimensional printing (3DP) is an emerging technology, offering the possibility for the development of dose-customized, effective, and safe solid oral dosage forms (SODFs). Although 3DP has great potential, it does come with certain limitations, and the traditional drug manufacturing platforms remain the industry standard. The consensus appears to be that 3DP technology is expected to benefit personalized medicine the most, but that it is unlikely to replace conventional manufacturing for mass production. The 3DP method, on the other hand, could prove well-suited for producing small batches as an adaptive manufacturing technique for enabling adaptive clinical trial design for early clinical studies. The purpose of this review is to discuss recent advancements in 3DP technologies for SODFs and to focus on the applications for SODFs in the early clinical development stages, including a discussion of current regulatory challenges and quality controls.
Topics: Printing, Three-Dimensional; Precision Medicine; Industry; Quality Control; Pharmaceutical Preparations; Technology, Pharmaceutical; Dosage Forms
PubMed: 38360287
DOI: 10.1016/j.ijpharm.2024.123902 -
Yakugaku Zasshi : Journal of the... 2015Drug products are developed to meet multiple targets, thereby increasing their value. Pharmaceutical scientists encounter several trade-offs during the development of... (Review)
Review
Drug products are developed to meet multiple targets, thereby increasing their value. Pharmaceutical scientists encounter several trade-offs during the development of novel oral formulations. These trade-offs are generated by their desire to supply the highest possible quality products under the prevailing conditions of limited time and cost, and feasible options. When there are two incompatible factors, it is sometimes difficult to dismiss one element. This is because a quality target product profile (QTPP) is critical for each product being developed, and all elements should basically be satisfied with the criteria. Therefore, technological innovation becomes important to overcome the trade-offs. This article introduces examples of such innovations which have been successful in doing this, as well as some encountered in the oral formulation development and in the selection of proper dosage forms. Based on these examples, points to be considered in order to produce the drug product are thoroughly discussed.
Topics: Administration, Oral; Dosage Forms; Drug Design; Humans; Solubility
PubMed: 25747218
DOI: 10.1248/yakushi.14-00228-2 -
AAPS PharmSciTech Dec 2011Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility,... (Review)
Review
Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability, and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water-soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g., as osmotic pumps) and/or hydrophobic CDs. New controlled delivery systems based on nanotechnology carriers (nanoparticles and conjugates) have also been reviewed.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Cyclodextrins; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Hydrophobic and Hydrophilic Interactions; Kinetics; Nanoparticles; Nanotechnology; Pharmaceutical Preparations; Solubility; Technology, Pharmaceutical
PubMed: 21948320
DOI: 10.1208/s12249-011-9690-2 -
Drug Delivery and Translational Research Feb 2023There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is... (Review)
Review
There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products.
Topics: Humans; Quality of Life; Liposomes; Suspensions; Excipients; Nanoparticles
PubMed: 35963928
DOI: 10.1007/s13346-022-01223-5 -
TheScientificWorldJournal 2021Extemporaneous compounding is a pharmacy practice to produce suitable pharmaceutical preparations when there are no commercially available, licensed, and age-specific...
BACKGROUND
Extemporaneous compounding is a pharmacy practice to produce suitable pharmaceutical preparations when there are no commercially available, licensed, and age-specific dosage forms. Compared to the use of authorized drugs, these preparations have significant risks. Stability issues are one of the major concerns during the preparation of extemporaneous formulations.
AIM
The aim of this work was to study the stability of pediatric extemporaneous formulations of commercially available conventional solid dosage forms by reviewing systematically the currently available stability studies.
METHOD
Articles were searched in the databases of the Web of Science, PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar. From all the searched articles, a total of 28 experimental studies reporting the stability of oral pediatric extemporaneous formulations were included based on the inclusion criteria. Oral extemporaneous formulations from commercially available dosage forms and pure drugs were considered. According to the United States and British Pharmacopeia (USP and BP), most extemporaneous formulations are accepted as chemically stable if they maintain ≥90% of the original drug amount, physically stable if there is no apparent change in physical property, and microbiologically stable if there is no growth of microorganisms in prepared formulations. . In this study, most extemporaneous pediatric oral formulations were chemically, physically, and microbiologically stable and retained more than 90% of the initial content. Very few studies did not include either a physical stability test or a microbiological stability test.
CONCLUSION
According to this systematic review, the chemical and physical instabilities as well as microbial growth on pediatric oral extemporaneous formulations are very rare in published experimental studies. Most studies show that extemporaneous preparations are stable at the ICH recommended storage conditions and duration. Generally, extemporaneously prepared oral formulations will be the promising option for child medications.
Topics: Administration, Oral; Child; Dosage Forms; Drug Stability; Humans; Pediatrics
PubMed: 34955693
DOI: 10.1155/2021/8523091