Chemical Modulation of Topical and Transdermal Permeation
Marc B. Brown, Adrian C. Williams in The Art and Science of Dermal Formulation Development, 2019
N-Methyl-2-pyrrolidone (NMP) and 2-pyrrolidone (2-P) are the most widely studied enhancers of this group. NMP is a polar aprotic solvent and is used to extract aromatic moieties from oils, olefins, and animal feeds. It is a clear liquid at room temperature and is miscible with most common solvents, including water and alcohols. Likewise, 2-P is miscible with many solvents, again including water and alcohols, and is a liquid above 25˚C. 2-pyrrolidone is also commonly used industrially and is an intermediate in the manufacture of the widely used pharmaceutical excipient polyvinylpyrrolidone. As with many penetration enhancers, the pyrrolidones tend to show greater enhancement effects with hydrophilic permeants than with lipophilic materials, although this may be attributable to the greater scope for enhancement of inherently poorly permeating hydrophilic drugs.
Application of Bioresponsive Polymers in Drug Delivery
Deepa H. Patel in Bioresponsive Polymers, 2020
In-situ polymer precipitation based systems are those where the drug is incorporated in solution of water insoluble, biodegradable polymer in biocompatible organic solvent. When such formulation is injected, the water miscible organic solvent dissipates and water penetrate to organic layer which results in phase separation and precipitation of polymer, at site of injection. Such a method was designed by ARTIX and designated as Atrigel technology [126]. Example of such technology is EligardTM, which contain the luteinizing hormone releasing hormone agonist leuprolide acetate and poly(lactide-co-glycolic acid) (PLGA) dissolved in N-methyl-2-pyrrolidone (NMP) [126, 127]. This system is used to reduce testosterone levels in dogs. The problem with such system is the bursting out drug release after injecting drug. To control burst effect, four factors should be taken into consideration: concentration of polymers in solvents [128], molecular weight of polymers, solvent used [129] and addition of surfactants [130]. Brodbeck et al. studied that protein release is affected by type of solution formed. They studied NMP, triacetin, and ethyl benzoate ternary phase system with PLGA and water. The formulation with NMP Pyrrolidone shows rapid phase inversion and high burst while formulations containing triacetin and ethyl benzoate give low phase inversion and reduced burst of protein [131, 132].
Chemical Permeation through Disposable Gloves
Robert N. Phalen, Howard I. Maibach in Protective Gloves for Occupational Use, 2023
Seven paint stripping formulations were tested against gloves by Stull et al.91 after passing degradation resistance screening tests to measure permeation with the ASTM F 739 method for continuous contact and the ASTM F 1383 for intermittent contact. Plastic laminate (2.7 mil or 0.069 mm) and butyl rubber (16 mil or 0.41 mm) were the most effective gloves against the majority of paint stripping formulations.91 Non-disposable NR (30 mil or 0.76 mm) gloves showed rapid permeation (<15 min) for solvent-based paint strippers, while BTs were greater than 2 h for dibasic ester-based paint strippers. More gloves resisted permeation by N-methyl-2-pyrrolidone and dibasic ester-based paint strippers than conventional solvent products such as methylene chloride, methanol, isopropanol, acetone, and toluene. However, more readily available disposable thinner gloves were not tested. These results were consistent with those of Zellers and Sulewiski,107 where butyl gloves were more protective than NR gloves even at different temperatures.
Synthetic biodegradable polyesters for implantable controlled-release devices
Published in Expert Opinion on Drug Delivery, 2022
Jinal U. Pothupitiya, Christy Zheng, W. Mark Saltzman
Microparticle depots are often produced by solvent evaporation or spray-drying techniques and can entrap both hydrophilic and hydrophobic materials [68,69]. These well-known processes allow for the encapsulation of heat-sensitive drugs. Drawbacks of microparticle depots include poor encapsulation efficiencies, heterogeneity in particle size, toxic effects resulting from residual organic solvents left behind from the preparation process, and unpredictable burst release of drugs due to improper entrapment [20]. With in situ forming gels [70,71], the injected material (a solution or suspension) gels after injection into the local tissue environment. In one version of this approach, the polymer-drug solution is prepared by dissolving the two components – plus other additives to help control release – in a biocompatible, water-miscible solvent such as N-methyl-2-pyrrolidone [72]. When injected into the target area, the solvent disperses into the aqueous tissue environment, causing the polymer to precipitate, entrapping the drug within the polymer matrix. Although this method has the benefit of simplicity, it can suffer drawbacks due to the unpredictable release of drugs, owing to the heterogeneous distribution of drugs within the matrix and the delay between polymer-drug precipitation and injection [73–76].
The clinical toxicity of imidacloprid self-poisoning following the introduction of newer formulations
Published in Clinical Toxicology, 2021
Varan Perananthan, Fahim Mohamed, Seyed Shahmy, Indika Gawarammana, Andrew Dawson, Nicholas Buckley
Neonicotinoids are nicotinic acetylcholine receptor (nAChR) agonists, inducing neuromuscular paralysis. These agents are highly selective for insect nAChRs over vertebrate nAChRs, explaining its low human toxicity [3]. However, there are case reports of neuro-psychiatric sequelae, rhabdomyolysis resulting in acute kidney injury, ischemic and metabolic encephalopathy, ventricular fibrillation, multi-organ failure and even death after exposure to imidacloprid [4–16]. These features may not be due to nicotinic effects alone as the solvents in imidacloprid preparations such as N-methyl-2-pyrrolidone (NMP) and dimethylsulfoxide also contributes to its toxicity [2]. In Sri Lanka, several new formulations of Imidacloprid with unknown solvents have been introduced since we last reported on clinical outcomes [1]. We herein describe the clinical manifestations of these newer products, and compare these with our earlier observations.
Effect of binary combinations of solvent systems on permeability profiling of pure agomelatine across rat skin: a comparative study with statistically optimized polymeric nanoparticles
Published in Drug Development and Industrial Pharmacy, 2020
Mahesh Shinde, Nikhil Bali, Shahadev Rathod, Megha Karemore, Pramod Salve
Agomelatine was a gratis sample from Mehta API Pvt. Ltd. (Mumbai, India). PLGA (Resomer 503H) was supplied as a research sample by Evonik Degussa Pvt. Ltd. (Mumbai, India). Pluronic F-68 and PVA were gifted by Himedia (Mumbai, India). Transcutol HP was supplied as a gift sample by Gattefosse (Saint-Priest, France). Ethanol was purchased from Changshu Hongsheng Fine Chemicals Ltd. (Changshu, China). PG was purchased from SRL (Mumbai, India). Oleic acid was purchased from Loba (Mumbai, India). N-Methyl-2-pyrrolidone was acquired from SD Fine (Mumbai, India). Isopropyl myristate was a gift sample from Mohini Organics Pvt. Ltd. (Mumbai, India). Dimethyl formamide was procured from Ranbaxy Fine Chemicals Ltd. (New Delhi, India). All other ingredients used were of analytical reagent grade.