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PDA Journal of Pharmaceutical Science... 2022Pre-filled syringes have simplified parenteral administration of protein drugs. To ensure an easy and consistent movement of the plunger, the inner glass container...
Pre-filled syringes have simplified parenteral administration of protein drugs. To ensure an easy and consistent movement of the plunger, the inner glass container surface is typically siliconized. For bake-on siliconization, emulsions are sprayed on and heat treated. Due to the European Union regulation REACh ( the use of certain emulsion components, partially constituting the gold standard Liveo 365 35% Dimethicone NF Emulsion (Liveo 365), becomes restricted and Liveo 366 35% Dimethicone NF Emulsion (Liveo 366) has been introduced as an alternative. This change may affect the handling properties as well as the silicone layer formed. The purpose of these studies was to identify any differences that may influence the stability and safety of the final drug/device combination product to enable the use of the new emulsion. We compared silicone emulsions Liveo 365 and Liveo 366 and dilutions focusing on 1) their general physical stability, 2) the thermal degradation process of the emulsions and their components, and 3) the resulting silicone layer concerning chemistry, morphology, and functionality. The results were linked to the assessment of the final product regarding particle formation and short-term stability. A comparison of the emulsions Liveo 365 and Liveo 366 for bake-on siliconization is presented to support the transition of the latter as it becomes mandatory with REACh. Our studies show that the two emulsions do not significantly differ with respect to handling and stability, the resultant silicone layer characteristics as well as its functionality. We conclude that the transition to the new emulsion will not significantly impact the final product or the layer performance upon storage and with respect to particle formation.
Topics: Emulsions; Hot Temperature; Proteins; Silicones; Syringes
PubMed: 35365551
DOI: 10.5731/pdajpst.2020.012640 -
AAPS PharmSciTech Jul 2022Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel...
Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.
Topics: Antineoplastic Agents; Cell Line, Tumor; Drug Stability; Emulsions; Etoposide; Excipients; Female; Humans; Oleic Acids; Ovarian Neoplasms; Polysorbates; Surface-Active Agents; Triglycerides
PubMed: 35773548
DOI: 10.1208/s12249-022-02329-2 -
AAPS PharmSciTech Jun 2022Topical drug delivery provides several benefits over other conventional routes by providing localizing therapeutic effects and also avoids the gastrointestinal tract... (Review)
Review
Topical drug delivery provides several benefits over other conventional routes by providing localizing therapeutic effects and also avoids the gastrointestinal tract circumventing the first-pass metabolism and enzymatic drug degradation. Being painless, the topical route also prevents the difficulties linked with the parenteral route. However, there are limitations to the current topical systems which necessitate the need for further research to find functional excipients to overcome these limitations. This review deals in depth with the ionic liquids concerning their physicochemical properties and applicability as well as their role in the arena of topical drug delivery in permeation enhancement, bioavailability enhancement of the drugs by solvation, and drug moiety modification. The review gives a detailed insight into the recent literature on ionic liquid-based topical formulations like ionic liquid-based emulsions, active pharmaceutical ingredient-ionic liquids, ionic liquid-based bacterial cellulose membranes, topical small interfering RNA (siRNA) delivery, and ionogels as a possible solutions for overcoming the challenges associated with the topical route. This review also takes into account the toxicological aspects and biomedical applications of ionic liquids.
Topics: Administration, Topical; Drug Delivery Systems; Emulsions; Excipients; Ionic Liquids
PubMed: 35676441
DOI: 10.1208/s12249-022-02313-w -
Molecules (Basel, Switzerland) Mar 2021In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical...
In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to -60 °C.
Topics: Cannabidiol; Drug Carriers; Drug Delivery Systems; Emulsifying Agents; Emulsions; Lipid Droplets; Nanoparticles; Particle Size; Phospholipids; Rapeseed Oil; Soybean Oil; Water
PubMed: 33800445
DOI: 10.3390/molecules26051469 -
Physical Review. E Aug 2020We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multilayer droplet where the drug...
We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multilayer droplet where the drug kinetics are described by a pure diffusive process through different liquid shells. The multilayer problem is described by a system of diffusion equations coupled via interlayer conditions imposing continuity of drug concentration and flux. Mass resistance is imposed at the outer boundary through the application of a surfactant at the external surface of the droplet. The two-dimensional problem is solved numerically by finite volume discretization. Concentration profiles and drug release curves are presented for three typical round-shaped (circle, ellipse, and bullet) droplets and the dependency of the solution on the mass transfer coefficient at the surface analyzed. The main result shows a reduced release time for an increased elongation of the droplets.
Topics: Drug Delivery Systems; Drug Liberation; Emulsions; Kinetics; Models, Theoretical
PubMed: 32942448
DOI: 10.1103/PhysRevE.102.023114 -
Molecules (Basel, Switzerland) May 2022In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was...
In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the , which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.
Topics: Administration, Cutaneous; Chitosan; Emulsions; Skin; Skin Absorption; Surface-Active Agents
PubMed: 35630660
DOI: 10.3390/molecules27103183 -
AAPS PharmSciTech Apr 2022Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum...
Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum corneum. Foams are topical delivery systems that have excellent patient compliance, acceptability, and preference. Therefore, this study aimed to investigate a foamable microemulsion as an alternative topical and transdermal dosage form for diclofenac sodium (DS). The physicochemical properties (optical clarity, percentage transmittance, homogeneity, consistency of formulation, particle size, zeta potential, conductivity, viscosity, and morphology, etc.) of the DS-loaded ME were investigated. The foam stability of both drug-free ME and DS-loaded ME was measured. The foam quality was evaluated, and the chemical stability over 90 days was determined. Franz diffusion cells were employed to assess the in vitro drug release of a foamed DS-loaded ME and compared with a commercial topical product. A foamable and stable DS-loaded ME that maintained small particle sizes and constant zeta potential and was transparent and translucent in appearance after 90 days was successfully produced. The foam of the DS-loaded ME was physically more stable compared to the drug-free foam. The foam had an increased drug release rate compared to the commercial product. The foamable DS-loaded ME has a great potential to enhance the transdermal delivery of DS after topical administration. Foamed DS-loaded ME is a promising alternative to the current topical formulation of DS.
Topics: Administration, Cutaneous; Diclofenac; Drug Liberation; Emulsions; Humans; Solubility
PubMed: 35378669
DOI: 10.1208/s12249-022-02258-0 -
Advanced Healthcare Materials Apr 2022Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties...
Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties have been adjusted to control the drug release kinetics and obtain desirable properties of PLGA-based drug delivery systems. The PLGA microparticle formation begins as soon as the drug/PLGA-dissolved in the organic solvent phase (oil phase) is exposed to the water phase. The initial skin (or shell) formation on the oil droplets occurs very quickly, sometimes in the matter of milliseconds, and studying the process has been difficult. The skin formation on the PLGA emulsion droplet surface that can affect the subsequent hardening steps is examined. PLGA droplets with different compositions are prepared. Using collimated light and a high-speed camera made it possible to detect the diffusion of acetonitrile from the oil phase into the water phase during the oil droplet formation. Although the skin formation is not visible on the surface of the oil phase droplet with the current setup, the droplet shapes, solid strand formation, and the difference in the spreading time suggest that the initial contact time between the oil and water phases in the range of a few seconds is critical to the properties of the skin.
Topics: Drug Liberation; Emulsions; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 34601826
DOI: 10.1002/adhm.202101427 -
Annals of Palliative Medicine Dec 2021The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures...
BACKGROUND
The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures (TNAs) by testing the percentage of fat residing in globules >5 µm (PFAT5) values.
METHODS
TNAs with different combinations of glucose (5% and 10%), amino acids (3.35 and 4.5 g/100 mL), Na+/K+ (100/39 mmol/L), Mg2+ (3.4 and 2.7 mmol/L), and fat emulsion (2.4%) were tested in triplicate at room temperature. The pH, mean droplet size (MDS), and PFAT5 were assessed at 0, 6, 12, 24, 36, and 48 h.
RESULTS
In all seven groups, the TNA globule distribution was uniform, the pH value fluctuated in the range of 5.93-6.06, and the MDS met the limit of the United States Pharmacopeia (USP) within 48 h. The PFAT5 value of the control group 0 without electrolytes was the lowest; group 1 added monovalent ions of 139 mmol/L was significantly higher (P<0.05) but without exceed the USP limit after 48 h. Groups 2 and 3 added Mg2+ 3.4 and 2.7 mmol/L respectively, based on group 1. Group 4 increased the amino acid concentration from 3.35% to 4.5% based on group 2, and group 5 reduced the glucose concentration from 10% to 5% based on group 4. Group 6 removed monovalent ions and retained only Mg2+ based on group 5. The PFAT5 values of group 2, 3, 4, and 5 exceeded the limit after 6 h and group 6 after 12 h. There was no statistical difference between group 2 and 4 (P>0.05) or between group 4 and 5 (P>0.05).
CONCLUSIONS
When the concentration of glucose is 10-25% and the amino acid is 2.5-4.5%, The addition of monovalent ions affects the stability of fat emulsion in TNAs, however when the concentrations of Na+ ≤100 mmol/L and K+ ≤39 mmol/L, the PFAT5 value will not exceed the USP limit within 24 h. Mg2+ has a significant effect, the PFAT5 value will exceed the USP limit after 6 h when the concentration ≥2.7 mmol/L, which may cause potential safety hazards.
Topics: Drug Stability; Fat Emulsions, Intravenous; Glucose; Humans; Nutrients; Particle Size
PubMed: 35016476
DOI: 10.21037/apm-21-3353 -
Current Pharmaceutical Design 2020Nanoemulsions (NEs) or nanometric-scaled emulsions are transparent or translucent, optically isotropic and kinetically stable heterogeneous system of two different...
Nanoemulsions (NEs) or nanometric-scaled emulsions are transparent or translucent, optically isotropic and kinetically stable heterogeneous system of two different immiscible liquids namely, water and oil stabilized with an amphiphilic surfactant having droplet size ranges up to 100 nm. They offer a variety of potential interests for certain applications: improved deep-rooted stability; excellent optical clarity; and, enhanced bioavailability due to its nanoscale of particles. Though there is still comparatively narrow insight apropos design, development, and optimization of NEs, which mainly stems from the fact that conventional characteristics of emulsion development and stabilization only partly apply to NEs. The contemporary article focuses on the nanoemulsion dosage form journey from concept to key application in drug delivery. In addition, industrial scalability of the nanoemulsion, as well as its presence in commercial and clinical practice, are also addressed.
Topics: Biological Availability; Emulsions; Nanoparticles; Surface-Active Agents; Water
PubMed: 32183664
DOI: 10.2174/1381612826666200317140600