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International Journal of Toxicology 2006The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo... (Comparative Study)
Comparative Study Review
The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used in 368 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. Reported here are the results of this effort, including maximum tolerated use levels by species, route, and duration of study, with accompanying dose limiting toxicity. Also included are basic chemical information and a review of available literature on each vehicle, as well as guidance on volume limits and pH by route and some basic guidance on nonclinical formulation development.
Topics: Animals; Databases, Factual; Drug Administration Routes; Drug Evaluation, Preclinical; Pharmaceutical Vehicles; Toxicity Tests
PubMed: 17132609
DOI: 10.1080/10915810600961531 -
Dermatology (Basel, Switzerland) 2023Drug patch test to identify cutaneous adverse drug reactions (CADRs) has been widely reported. Appropriate vehicles can improve the ability of drug delivery and...
BACKGROUND
Drug patch test to identify cutaneous adverse drug reactions (CADRs) has been widely reported. Appropriate vehicles can improve the ability of drug delivery and significantly increase positive reaction of drug patch tests.
OBJECTIVE
The aim of this study was to evaluate the efficacy of drug patch tests using 0.9% saline vehicle in comparison with other traditional vehicles in CADRs.
METHOD
All patients were patch tested with suspected drugs using 10-30% concentration of the commercialized form of drugs diluted in 0.9% saline, petrolatum, and water.
RESULT
Of 100 patients with CADRs, 54 of those had at least one positive drug patch test. In terms of vehicles used, 43 patients had positive drug patch test with saline as compared to 35 with water (p = 0.485) and 25 with petrolatum (p = 0.007). Among CADRs subgroup, saline rendered significantly higher positive rate when compared with petrolatum in drug rash with eosinophilia and systemic symptom (DRESS) (70% vs. 20%, p = 0.025), maculopapular rash (MP) (52.4% vs. 31%, p = 0.046), and lichenoid drug eruption (46.7% vs. 0.0%, p = 0.002). 12/54 (22.2%) of CADRs patients had positive reaction with saline alone. Among these patients, 4/12 (33.3%) were lichenoid drug reaction, 3/12 (25%) were DRESS, and 2/12 (16.7%) were MP rash. Allopurinol was the drug giving positive patch test only with saline.
CONCLUSION
Appropriate vehicles are essential to obtain the positive drug patch test. Using saline as a vehicle can increase the positive reaction of drug patch test, particularly in lichenoid drug eruption. We recommend the use of saline as another traditional vehicle in drug patch test.
Topics: Humans; Patch Tests; Saline Solution; Drug Eruptions; Pharmaceutical Preparations; Exanthema; Lichen Planus
PubMed: 36599331
DOI: 10.1159/000528919 -
Pharmaceutics Jun 2018Wound management, in addition to presenting a significant burden to patients and their families, also contributes significantly to a country’s healthcare costs.... (Review)
Review
Wound management, in addition to presenting a significant burden to patients and their families, also contributes significantly to a country’s healthcare costs. Treatment strategies are numerous, but in most cases not ideal. Hydrogels, three-dimensional polymeric materials that can withstand a great degree of swelling without losing structural integrity, are drawing great attention for their use as topical wound management solutions in the form of films and as vehicles for drug delivery, due to their unique properties of high water content, biocompatibility, and flexibility. Hydrogels, both naturally and synthetically derived, can be tuned to respond to specific stimuli such as pH, temperature and light and they are ideally suited as drug delivery vehicles. Here we provide a brief overview of the history and characteristics of hydrogels, assess their uses in wound management and drug delivery, and compare them with other types of common drug delivery vehicle.
PubMed: 29899219
DOI: 10.3390/pharmaceutics10020071 -
Toxicologic Pathology Apr 2016Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal... (Review)
Review
Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal nonclinical studies, in lieu of the dog or nonhuman primate, for compounds delivered via standard systemic routes of administration. Little is known about the tolerability of different excipients in minipigs; sharing knowledge of excipient tolerability and compositions previously used in nonclinical studies may avoid testing of inadequate formulations, thereby contributing to reduced animal usage. This article reviews vehicles employed in the Göttingen(®)minipig based on the combined experience from a number of pharmaceutical companies and contract research organizations. The review includes vehicles tolerated for single or multiple dosing by the Göttingen minipig, some of which are not appropriate for administration to other common nonrodent species (e.g., dogs). By presenting these data for dermal, oral, subcutaneous, and intravenous routes of administration, studies to qualify these vehicles in minipigs can be minimized or avoided. Additionally, investigators may more frequently consider using the minipig in place of higher species if the tolerability of a vehicle in the minipig is known.
Topics: Animals; Biomedical Research; Drug Administration Routes; Drug Discovery; Excipients; Pharmaceutical Vehicles; Swine; Swine, Miniature
PubMed: 26674803
DOI: 10.1177/0192623315613088 -
Journal of Drugs in Dermatology : JDD Feb 2019It has been said that the best treatment for a given patient is the one that the patient will actually use. The comment, often spoken with humor, actually underscores...
It has been said that the best treatment for a given patient is the one that the patient will actually use. The comment, often spoken with humor, actually underscores several important aspects of dermatology care today. Foremost is the fact that patient adherence (as influenced by their satisfaction with treatment) is a critical driver of clinical success. Additionally, dermatologists now often have a range of vehicle formulations from which to select treatment.
Topics: Administration, Cutaneous; Dermatologic Agents; Dermatology; Drug Delivery Systems; Humans; Patient Compliance; Pharmaceutical Vehicles; Skin Diseases
PubMed: 30811152
DOI: No ID Found -
Future Medicinal Chemistry Jul 2019Dextran has become a hot research topic in drug vehicle material because of its biodegradable, nonspecific cell adhesion, resistance to protein adsorption, low price and... (Review)
Review
Dextran has become a hot research topic in drug vehicle material because of its biodegradable, nonspecific cell adhesion, resistance to protein adsorption, low price and ease of structural modification. The fate and changes of dextran in vivo are not fully understood. It is helpful to guide the design and modification of dextran drug vehicles to clarify the changes in the morphology, metabolism and function of drug targets. With the deep understanding of dextran and the emergence of new functional dextran derivatives, its application in nanodrug delivery systems will be more and more, clinically applicable delivery systems may also be available.
Topics: Biocompatible Materials; Carbohydrate Conformation; Dextrans; Drug Carriers; Drug Delivery Systems; Gene Transfer Techniques; Humans
PubMed: 31469330
DOI: 10.4155/fmc-2018-0586 -
Nanomedicine (London, England) Jul 2020
Topics: Drug Delivery Systems; Nanoparticles; Neoplasms; Pharmaceutical Preparations; Polyethylene Glycols
PubMed: 32576101
DOI: 10.2217/nnm-2020-0152 -
Journal of Drugs in Dermatology : JDD Apr 2014Topical treatment is a pillar of dermatologic practice. The delivery of drug by a topical vehicle is dependent on complex physical chemistry and on how well patients... (Review)
Review
Topical treatment is a pillar of dermatologic practice. The delivery of drug by a topical vehicle is dependent on complex physical chemistry and on how well patients apply the product. The potency of topical agents is not solely dependent on the concentration of active drug in the vehicle. A corticosteroid molecule may have vastly different potency depending on what vehicle is used to deliver it. Similarly, a new gel vehicle is able to deliver considerably more active antifungal than an older vehicle technology and may represent a promising vehicle for other novel formulations. The use of new vehicles can provide more effective means for treating patients with skin disease.
Topics: Administration, Cutaneous; Excipients; Gels; Humans; Medication Adherence; Skin Diseases
PubMed: 24719061
DOI: No ID Found -
International Journal of Toxicology 2016Formulation of nonclinical evaluations is a challenge, with the fundamental need to achieve multiples of the clinical exposure complicated by differences in species and... (Review)
Review
Formulation of nonclinical evaluations is a challenge, with the fundamental need to achieve multiples of the clinical exposure complicated by differences in species and routes of administration-specific tolerances, depending on concentrations, volumes, dosing regimen, duration of each administration, and study duration. Current practice to approach these differences is based on individual experience and scattered literature with no comprehensive data source (the most notable exception being our 2006 publication on this same subject). Lack of formulation tolerance data results in excessive animal use, unplanned delays in the evaluation and development of drugs, and vehicle-dependent results. A consulting firm, a chemical company, and 4 contract research organizations conducted a rigorous data mining operation of vehicle data from studies dating from 1991 to 2015, enhancing the data from this author's 2006 publication (3 of the six 2015 contributors were also 2006 contributors). Additional data were found in the published literature. The results identified 108 single-component vehicles (and 305 combination formulations) used in more than 1,040 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, pig, chick embryo, and cat) by multiple routes for a wide range of study durations. The tabulated data include maximum tolerated use levels by species, route, duration of study, dose-limiting toxicity where reported, review of the available literature on each vehicle, guidance on syringe selection, volume and pH limits by route with basic guidance on nonclinical formulation development, and guidance on factors to be considered in nonclinical route selection.
Topics: Animals; Dose-Response Relationship, Drug; Drug Administration Routes; Species Specificity; Toxicity Tests
PubMed: 26755718
DOI: 10.1177/1091581815622442 -
Advanced Drug Delivery Reviews Jul 2023Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and... (Review)
Review
Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and physiological barriers while minimising tissue toxicity has restricted developments in this field. Aqueous vehicles have traditionally been used, which typically require several additives and preservatives to achieve physiologically compatible and sterile eyedrops, elevating their toxicity potential. Non-aqueous vehicles have been suggested as efficient alternatives for topical drug delivery as they can address many of the limitations associated with conventional aqueous eyedrops. However, despite their obvious advantages, non-aqueous eyedrops remain poorly researched and few non-aqueous formulations are currently available in the market. This review challenges the conventional hypothesis that aqueous solubility is a prerequisite to ocular drug absorption and establishes a rationale for using non-aqueous vehicles for ocular drug delivery. Recent advances in the field have been detailed and future research prospects have been explored, pointing towards a paradigm shift in eyedrop formulation in the near future.
Topics: Humans; Administration, Topical; Eye; Drug Delivery Systems; Ophthalmic Solutions
PubMed: 37178927
DOI: 10.1016/j.addr.2023.114867