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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 -
Pharmaceutical Development and... Nov 2020Silymarin has a short half-life (4-6 hours) which leads to necessity of frequent administration. Besides, it suffers from intestinal degradation. Thus, our study aims...
Silymarin has a short half-life (4-6 hours) which leads to necessity of frequent administration. Besides, it suffers from intestinal degradation. Thus, our study aims to formulate encapsulated floating microspheres using different polymers as HPMC, EC and a blend of them. Emulsion solvent evaporation technique was applied for preparation of microspheres. Parameters considered during preparation are drug: polymer ratio and emulsifier concentration. Selected formulations were characterized by SEM and subjected for assessment by drug entrapment efficiency, buoyancy for 12 hr, drug release, kinetics of release and stability. bio-equivalence study was performed using albino rabbits. Formula F24 (treatment II) exhibited high % buoyancy (73.4), higher t (190.7 day), high C (1021.3 ng/ml) and T (6 h) with a significant difference between it and treatment I (Silymarin plus) after carrying out ANOVA study. Also formula F24 exhibited MRT (hr) equal 9.44 ± 0.03 and high relative bioavailability RB% (227%), which indicates promising microspheres that could be used for effective management of liver disease.
Topics: Animals; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Liberation; Emulsions; Microspheres; Polymers; Rabbits; Silymarin
PubMed: 32654568
DOI: 10.1080/10837450.2020.1795192 -
The AAPS Journal Oct 2023Advances in drug delivery have been accelerated with the addition of polymeric drug carriers. Direct delivery to a target site is a promising step in developing...
Advances in drug delivery have been accelerated with the addition of polymeric drug carriers. Direct delivery to a target site is a promising step in developing effective drug and gene therapies to treat disease. The efficacy of these drug carriers heavily relies on cell uptake without compromising critical cellular processes that promote cell viability. Drug release from biodegradable polymers is mediated largely by polymer degradation, and therefore the rate of polymer degradation dictates the feasibility of drug delivery applications. Traditionally, poly(caprolactone) (PCL) has only been used in long-term biomedical applications because the degradation time is much slower than other polymers. However, the biocompatibility of this polymer and the potential for longer delivery windows renders it a promising polymer candidate for drug delivery. In this work, we outline sixteen emulsion solvent evaporation preparation methods for PCL nanoparticles and microparticles to develop particles between 300 nm and 1.7 μm and with zeta potentials of -1.8 mV. We further investigated particles in a size range suitable for systemic tumor delivery and inhaled aerosol delivery to determine cell biocompatibility with the polymer in lung adenocarcinoma, endometrial adenocarcinoma, and human embryonic kidney cells. We determined these particles aren't detrimental to cell viability below particle monolayer coverage atop cells and therefore these formulations hold promise for the next stage of development as sustained-release drug delivery carriers.
Topics: Humans; Emulsions; Drug Delivery Systems; Polyesters; Drug Carriers; Polymers; Nanoparticles; Particle Size; Microspheres
PubMed: 37891411
DOI: 10.1208/s12248-023-00869-4 -
AAPS PharmSciTech Apr 2024Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability.... (Review)
Review
Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes.
Topics: Phospholipids; Humans; Drug Delivery Systems; Neoplasms; Antineoplastic Agents; Solubility; Animals; Chemistry, Pharmaceutical; Biological Availability; Emulsions; Drug Carriers; Drug Compounding
PubMed: 38664316
DOI: 10.1208/s12249-024-02813-x -
AAPS PharmSciTech Jun 2023Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort....
Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort. However, the sluggish drug absorption, poor skin dissolution, and lengthy time lags of DMN have limited its potential uses. The aim of this study was to design a novel DMN system for the administration of the poorly water-soluble drug, estradiol (E2), with fast skin penetration and a stable release rate for a long time. DMN containing E2 emulsion (E2-EM-DMN) and traditional DMN (T-DMN) were prepared. Rat skin was used for penetration test and guinea pig skin was used for skin irritation experiment. The drug release profiles and stability properties of these two kinds of DMNs were also investigated. High performance liquid chromatography was employed to determine the E2 content in DMN. The E2 concentration in rat plasma was achieved by a newly developed liquid chromatography-mass spectrometry method that was fast, reproducible, and specific. The height of E2-EM-DMN and T-DMN was 600 μm. The drug loading of the E2-EM-DMN and T-DMN was 667.30 ± 7.21 μg/patch and 672.56 ± 6.98 μg/patch. E2-EM-DMN possessed enough mechanical strength to penetrate the skin and caused no irritation to the skin. E2-EM-DMN could release the drug more rapidly and more continuously than T-DMN. E2-EM-DMN had good pharmaceutical stability. In summary, the E2-EM-DMN showed reliable quality and superior release performance. Emulsion-embedded DMN is an ideal transdermal delivery system for drugs.
Topics: Rats; Animals; Estradiol; Delayed-Action Preparations; Emulsions; Administration, Cutaneous; Skin; Drug Delivery Systems; Inflammation; Needles
PubMed: 37353673
DOI: 10.1208/s12249-023-02604-w -
International Journal of Pharmaceutics Jan 2022Due to the superior safety and therapeutic efficacy, clopidogrel (CLP) has been widely used to prevent postoperative thrombosis. However, limitations of delayed...
Due to the superior safety and therapeutic efficacy, clopidogrel (CLP) has been widely used to prevent postoperative thrombosis. However, limitations of delayed absorption and metabolic activation of clopidogrel after oral administration hinder its clinic use for acute thrombosis treatment in percutaneous coronary intervention (PCI). Although clopidogrel aqueous injection systems were designed and developed, chemical instability under physiological condition or vascular irritation remains to be solved. In this study, we aim to prepare an injectable clopidogrel loaded submicron emulsion to overcome the drawbacks of conventional clopidogrel aqueous formulation and improve the antiplatelet aggregation effects. Results showed that this delivery system exerted inspiring features including uniform particle size, higher drug loading capacity and sustained drug release behavior. It can dramatically upgrade the formulation stability and prevent the drug degradation under sterilization or higher pH environments. No remarkable droplet size increase or drug content decrease was observed during storage. Compared to CLP tablet, the peak drug concentration (C) and area under the curve (AUC) of CLP emulsion increased by 12.01-fold and 4.69-fold, respectively. Most importantly, it exerted excellent in vivo anti-thrombotic effect on numerous designed animal models. Conclusively, submicron emulsion is a promising delivery system for improving clopidogrel stability and anti-thrombotic efficacy.
Topics: Animals; Clopidogrel; Emulsions; Particle Size; Percutaneous Coronary Intervention; Thrombosis
PubMed: 34848363
DOI: 10.1016/j.ijpharm.2021.121323 -
Journal of AOAC International Sep 2023The replacement of traditional oils with a camphor and menthol-based eutectic mixture is done to prepare oil-less emulsion-like dispersions for co-delivery of...
Analytical Quality by Design-Driven RP-HPLC Method Conditions to Concomitantly Determine Cinnarizine and Morin Hydrate in Combined Drug Solution and Dual Drug-Loaded Formulations.
BACKGROUND
The replacement of traditional oils with a camphor and menthol-based eutectic mixture is done to prepare oil-less emulsion-like dispersions for co-delivery of cinnarizine (CNZ) and morin hydrate (MH) for managing Meniére's disease (MD). Since two drugs are loaded into the dispersions, the development of a suitable reverse phase-high performance liquid chromatography (RP-HPLC) method for their simultaneous analysis becomes inevitable.
OBJECTIVE
By applying the analytical quality by design (AQbD) approach, the RP-HPLC method conditions were optimized for the concomitant determination of two drugs.
METHODS
The systematic AQbD started with identifying critical method attributes (CMA) through an Ishikawa fishbone diagram, risk estimation matrix, and risk priority number-based failure mode effect analysis followed by screening using fractional factorial design and optimization by face-centered central composite design. The concomitant determination of two drugs by the optimized RP-HPLC method condition was substantiated via specificity checking using combined drug solution, drug entrapment efficiency, and in vitro release of the two drugs from emulsion-like dispersions.
RESULTS
The AQbD optimized RP-HPLC method conditions revealed the retention time for CNZ and MH at 5.017 and 5.323, respectively. The studied validation parameters were found within the ICH-prescribed limits. Exposing the individual drug solutions to acidic and basic hydrolytic conditions yielded extra chromatographic peaks for MH, probably due to the degradation of MH. The DEE % values of 87.40 ± 4.70 and 74.79 ± 2.94, respectively, were noticed for CNZ and MH in emulsion-like dispersions. More than 98% CNZ and MH release was occurred from emulsion-like dispersions within 30 min post-dissolution in artificial perilymph.
CONCLUSIONS
Overall, the AQbD approach could be helpful for systematic optimization of RP-HPLC method conditions to estimate concomitantly other therapeutic moieties.
HIGHLIGHTS
The proposed article shows the successful application of AQbD for the optimization of RP-HPLC method conditions to concomitantly estimate CNZ and MH in combined drug solution and dual-drug-loaded emulsion-like dispersions.
Topics: Cinnarizine; Chromatography, High Pressure Liquid; Emulsions; Drug Compounding
PubMed: 37279742
DOI: 10.1093/jaoacint/qsad068 -
International Journal of Nanomedicine 2023The aim of this study was to develop a liposome gel containing -tetrahydropalmatine (-THP) and evaluate its transdermal properties.
PURPOSE
The aim of this study was to develop a liposome gel containing -tetrahydropalmatine (-THP) and evaluate its transdermal properties.
METHODS
A L (4) orthogonal experiment was conducted to optimize the preparation of -THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M membrane, respectively. The metabolism of -THP in liver and skin S9 fractions was also studied.
RESULTS
The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and -THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of -41.27 mV. Both the -THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (C) of -THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (t) was 1.2 hours. The relative bioavailability of -THP in the liposome gel was 233.8% compared to the emulsion. The concentration of -THP (prepared in PBS) decreased at a rate of 0.0067 μg/mL/min in the liver S9 fraction and 0.0027 μg/mL/min in the skin S9 fraction, however, this difference was not observed when -THP was encapsulated in liposomes. -THP passed through the Strat-M membrane at a rate of 0.0032 mg/cm/h and 0.002 mg/cm/h for the emulsion and liposome gel, respectively.
CONCLUSION
The optimal process for the preparation of -THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for -THP during storage.
Topics: Animals; Rats; Liposomes; Emulsions; Skin; Lecithins
PubMed: 37600118
DOI: 10.2147/IJN.S422305 -
Journal of Drug Targeting Aug 2022Oral delivery is the most desired route of drug administration and it can be more beneficial for patients suffering from chronic diseases wherein frequent parenteral...
Oral delivery is the most desired route of drug administration and it can be more beneficial for patients suffering from chronic diseases wherein frequent parenteral administration of proteins such as insulin and calcitonin is required. The Biopharmaceutics Classification System (BCS) class II drugs show low aqueous solubility and high permeability whereas BCS class IV drugs suffer from low aqueous solubility and low permeability. Additionally, biologic drugs are highly sensitive to presence of bioenzymes and bile salts when administered orally. Self-emulsifying drug delivery system (SEDDS) is a thermodynamically stable lipid formulation that enhances oral absorption of active ingredients the opening of tight junctions, increasing the membrane fluidity and thus overcomes the physiological barriers like viscous mucus layer, strong acid conditions and enzymatic degradation. An understanding of different theories that govern SEDDS formation and drug release can help in formulating a highly stable and effective drug delivery system. Poorly permeable drugs such as chlorpromazine require modification using methods like hydrophobic ion pairing, complexation with phospholipids, etc. to enable high entrapment efficiency, which is discussed in the article. Additionally, the article gives an overview of the influence of polymers, length of fatty acids chain and zeta potential in enhancing permeation across the intestinal membrane.
Topics: Administration, Oral; Drug Delivery Systems; Emulsions; Humans; Hydrophobic and Hydrophilic Interactions; Permeability; Solubility
PubMed: 35451898
DOI: 10.1080/1061186X.2022.2069783 -
ACS Macro Letters Jul 2021Confined self-assembly of block copolymers (BCPs) is effective to manipulate various shapes of particles. In emulsion confined self-assembly, reversibly light-trigged...
Confined self-assembly of block copolymers (BCPs) is effective to manipulate various shapes of particles. In emulsion confined self-assembly, reversibly light-trigged switchable BCP particles are extremely expected, yet rarely reported. Herein, a novel strategy is developed to realize reversibly light-responsive shape-transformation of BCP particles by constructing functional surfactants with light-active azobenzene (azo) groups in the confined self-assembly of BCPs within emulsion droplet. Ultraviolet and visible lights can reversibly modulate the amphiphilicity and interfacial affinity of the surfactants to different blocks, triggering the reversible microphase structure transformation of BCP particles with high temporal-spatial resolution. We can realize shape and morphological transitions of BCP particles from onion-shaped spherical particles to striped ellipsoids and, ultimately, to inverse onion-like particles by ultraviolet irradiation. More importantly, this shape transformation is reversible by the irradiation of visible light, attributed to the reversible - isomerization of azo groups. We also demonstrate that the light-triggered shape transformation of BCP particles can be employed in a controllable drug release through a noncontacted and programmed manner, showing promising potential in clinic and biomedicine.
Topics: Drug Liberation; Emulsions; Light; Polymers; Surface-Active Agents
PubMed: 35549210
DOI: 10.1021/acsmacrolett.1c00356