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The AAPS Journal Jul 2016Cell-based therapy is the fastest growing segment of regenerative medicine, a field that promises to cure diseases not treated by other small molecules or biological... (Review)
Review
Cell-based therapy is the fastest growing segment of regenerative medicine, a field that promises to cure diseases not treated by other small molecules or biological drugs. The use of living cells as the active medicinal ingredient present great opportunities to deliver treatment that can trigger the body's own capacity to regenerate damaged or diseased tissue. Some of the challenges in controlling the quality of the finished cell-therapy product relate to the use of a variety of raw materials including excipients, process aids, and growth promotion factors. The quality of these materials is critical for ensuring the safety and quality of the finished therapeutic products. This review will discuss some of the challenges and opportunities associated with the qualification of excipients as well as that of the ancillary materials used in manufacturing.
Topics: Chemistry, Pharmaceutical; Excipients; Humans
PubMed: 27233803
DOI: 10.1208/s12248-016-9935-9 -
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 -
Molecules (Basel, Switzerland) Feb 2022β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing...
β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO and HO. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development.
Topics: Animals; Chromatography, High Pressure Liquid; Excipients; Male; Rats; Rats, Wistar; Tandem Mass Spectrometry; Tissue Distribution; beta-Cyclodextrins
PubMed: 35164401
DOI: 10.3390/molecules27031138 -
Molecules (Basel, Switzerland) Oct 2023It is widely recognized that many active pharmaceutical ingredients (APIs) have a disagreeable taste that affects patient acceptability, particularly in children.... (Review)
Review
It is widely recognized that many active pharmaceutical ingredients (APIs) have a disagreeable taste that affects patient acceptability, particularly in children. Consequently, developing dosage forms with a masked taste has attracted a lot of interest. The application of cyclodextrins as pharmaceutical excipients is highly appreciated and well established, including their roles as drug delivery systems, solubilizers and absorption promoters, agents that improve drug stability, or even APIs. The first work describing the application of the taste-masking properties of CDs as pharmaceutical excipients was published in 2001. Since then, numerous studies have shown that these cyclic oligosaccharides can be effectively used for such purposes. Therefore, the aim of this review is to provide insight into studies in this area. To achieve this aim, a systematic evaluation was conducted, which resulted in the selection of 67 works representing both successful and unsuccessful works describing the application of CDs as taste-masking excipients. Particular attention has been given to the methods of evaluation of the taste-masking properties and the factors affecting the outcomes, such as the choice of the proper cyclodextrin or guest-host molar ratio. The conclusions of this review reveal that the application of CDs is not straightforward; nevertheless, this solution can be an effective, safe, and inexpensive method of taste masking for pharmaceutical purposes.
Topics: Child; Humans; Pharmaceutical Preparations; Excipients; Cyclodextrins; Taste; Chemistry, Pharmaceutical; Solubility
PubMed: 37836807
DOI: 10.3390/molecules28196964 -
Journal of Pharmaceutical Sciences Jan 2023This study examined physical stability of spray freeze dried (SFD) bovine serum albumin (BSA) solids produced using the radio frequency (RF)-assisted drying technique....
This study examined physical stability of spray freeze dried (SFD) bovine serum albumin (BSA) solids produced using the radio frequency (RF)-assisted drying technique. BSA formulations were prepared with varying concentrations of trehalose and mannitol, using an excipient-free formulation as control. These formulations were produced using either traditional ultrasonic spray freeze drying (SFD) or RF-assisted ultrasonic spray freeze drying (RFSFD). The dried formulations were then characterized using Karl Fischer moisture content measurement, powder X-ray diffraction (PXRD), size exclusion chromatography (SEC), and solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS). Moisture content did not have a good correlation with the physical stability of the formulations measured by SEC. ssHDX-MS metrics such as deconvoluted peak areas of the deuterated samples showed a satisfactory correlation (R = 0.914) with the SEC stability data. RFSFD improved the stability of formulations with 20 mg/ml of trehalose and no mannitol, and had similar stability with all other formulations as compared to SFD. This study demonstrated that RFSFD technique can significantly reduce the duration of primary drying cycle from 48.0 h to 27.5 h while maintaining or improving protein physical stability as compared to traditional lyophilization.
Topics: Trehalose; Ultrasonics; Freeze Drying; Excipients; Powders; Mannitol; Serum Albumin, Bovine
PubMed: 36181875
DOI: 10.1016/j.xphs.2022.09.024 -
PloS One 2022The use of starch, a natural polymeric material, and derivatives thereof is based on its adhesive, thickening, gelling, swelling, and film-forming properties, as well as...
The use of starch, a natural polymeric material, and derivatives thereof is based on its adhesive, thickening, gelling, swelling, and film-forming properties, as well as its ready availability. The objective of this research work is to develop an effective propylated Dioscorea abyssinica starch (PDAS) as a hydrophobic excipient for pharmaceutical applications with a reasonable price. This paper reports on the synthesis, characterization, and in vivo safety evaluation of PDAS. Native Dioscorea abyssinica starch (NDAS) was modified to its propylated form with propionic anhydride and characterized. Crystallinity, morphological structure, thermal behavior, solubility, and safety of PDAS were evaluated using x-ray diffraction, SEM, thermogravimetric, gravimetric, and toxicity studies, respectively. Propionyl content and degree of substitution (DS) of starch increased significantly (p < 0.05) with an increase in reaction time and temperature. Propionyl content and DS of starch increased significantly (p < 0.05) with a decrease in the ratio of starch to pyridine and starch to propionic anhydride in the reaction medium. FTIR spectra of PDAS indicated that hydroxyl groups participated in the propylation reaction. X-ray diffraction results showed that the chemical modification destroyed the crystalline structure of the NDAS. SEM of NDAS showed a rounded shape which became irregular after propylation. Thermogravimetric curves revealed that all the PDAS samples decomposed at higher temperatures than their native counterparts. At higher DS, swelling power and solubility in an aqueous environment significantly (p < 0.05) decreased below that of the native starch. PDAS with high DS, were soluble in organic solvents at room temperature. But PDAS with lower DS didn't dissolve in all types of organic solvents used. PDAS (DS = 2.842) in distilled water did not produce adverse effects in rats. Based on the results obtained, it can be concluded that PDAS can be considered as a generally safe excipient and fulfills the physicochemical properties of a hydrophobic excipient.
Topics: Animals; Rats; Dioscorea; Starch; Excipients; Solvents
PubMed: 36441719
DOI: 10.1371/journal.pone.0276965 -
Journal of Pharmaceutical Sciences Dec 2015Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to...
Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232> and International Conference on Harmonization's Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present.
Topics: Drug Contamination; Elements; Excipients; Mass Spectrometry; Microwaves; Pharmaceutical Preparations
PubMed: 26398581
DOI: 10.1002/jps.24650 -
Lung Oct 2020Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine... (Review)
Review
Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine are more important to the patient than the pharmacology of the active ingredient. Excipients are generally defined as any ingredient in a medicine other than the active ingredient. In most medicines excipients play a supportive role in delivering the medicine, but in the case of cough medicines, excipients have more important and complex roles and they can also be the main active ingredient of the cough medicine as menthol, glycerol, and sugars, which are declared as active ingredients. This review searched the United Kingdom electronic medicines compendium (emc) and found over 100 excipients in 60 different liquid formulations of over the counter cough medicines. The excipients were divided into functional groups: sweeteners, thickeners, flavors, colors, antimicrobials, and buffers, and the incidence and function of the different excipients is discussed. When considering the efficacy of a cough medicine, clinicians and pharmacists tend to think of the pharmacology of antitussives such as dextromethorphan or expectorants such as guaifenesin, and they rarely consider the role of excipients in the efficacy of the medicine. This review discusses the functions and importance of excipients in cough medicines and provides some new information for clinicians, pharmacists, and all interested in the treatment of cough when considering the composition and efficacy of a cough medicine.
Topics: Humans; Antitussive Agents; Cough; Drug Compounding; Excipients; Nonprescription Drugs; Pharmaceutical Solutions; Treatment Outcome
PubMed: 32889596
DOI: 10.1007/s00408-020-00390-x -
European Journal of Pharmaceutics and... Sep 2022Parenteral formulations are indispensable in clinical practice and often are the only option to administer drugs that cannot be administrated through other routes, such... (Review)
Review
Parenteral formulations are indispensable in clinical practice and often are the only option to administer drugs that cannot be administrated through other routes, such as proteins and certain anticancer drugs - which are indispensable to treat some of the most prevailing chronic diseases worldwide (like diabetes and cancer). Additionally, parenteral formulations play a relevant role in emergency care since they are the only ones that provide an immediate action of the drug after its administration. However, the development of parenteral formulations is a complex task owing to the specific quality and safety requirements set for these preparations and the intrinsic properties of the drugs. Amongst all the strategies that can be useful in the development of parenteral formulations, the formation of water-soluble host-guest inclusion complexes with cyclodextrins (CDs) has proven to be one of the most advantageous. CDs are multifunctional pharmaceutical excipients able to form water-soluble host-guest inclusion complexes with a wide variety of molecules, particularly drugs, and thus improve their apparent water-solubility, chemical stability, and bioavailability, to make them suitable for parenteral administration. Besides, CDs can be employed as building blocks of more complex injectable drug delivery systems with enhanced characteristics, such as nanoparticles and supramolecular hydrogels, that has been found particularly beneficial for the delivery of anticancer drugs. However, only a few CDs are considered safe when parenterally administered, and some of these types are already approved to be used in parenteral dosage forms. Therefore, the application of CDs in the development of parenteral formulations has been a more common practice in the last few years, due to their significant worldwide acceptance by the health authorities, promoting the development of safer and more efficient injectable drug delivery systems.
Topics: Cyclodextrins; Drug Compounding; Drug Delivery Systems; Excipients; Hydrogels; Solubility; Water
PubMed: 35868490
DOI: 10.1016/j.ejpb.2022.07.007 -
The AAPS Journal Dec 2012The aim of the present paper is to summarize the revised European Union (EU) Guideline on the Investigation of Bioequivalence and to discuss critically with respect to... (Review)
Review
The aim of the present paper is to summarize the revised European Union (EU) Guideline on the Investigation of Bioequivalence and to discuss critically with respect to previous European requirements and present US Food and Drug Administration guidelines its more relevant novelties such as the following: in order to facilitate the development of generic medicinal products, the EU guideline includes the eligibility for Biopharmaceutics Classification System (BCS)-based biowaivers not only for BCS class I drugs but also for class III drugs with tighter requirements for dissolution and excipient composition. The permeability criterion of BCS classification has been substituted with human absorbability, as per the Biopharmaceutical Drug Disposition Classification System. The widening of the acceptance range for C (max) is possible only for highly variable reference products with an additional clinical justification. This scaled widening is carried out with a proportionality constant of 0.760 which is more conservative than the FDA approach and maintains the consumer risk at a 5% level when the intra-subject CV is close to 30%, due to the smooth transition between the scaled and the constant criteria. The guideline allows for the possibility of two-stage designs to obtain the necessary information on formulation differences and variability from interim analyses as a part of the pivotal bioequivalence study, instead of undertaking pilot studies. The guideline also specifies that the statistical analyses should be performed considering all factors as fixed, which has implications in the case of replicate designs.
Topics: Drug Design; Drugs, Generic; European Union; Excipients; Guidelines as Topic; Humans; Pharmaceutical Preparations; Solubility; Therapeutic Equivalency; United States; United States Food and Drug Administration
PubMed: 22826032
DOI: 10.1208/s12248-012-9382-1