Control of encapsulation efficiency and morphology of poly(lactide-co-glycolide) microparticles with a diafiltration-driven solvent extraction process.

The removal of organic solvents during the preparation of biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by an O/W- solvent extraction/evaporation process was investigated and controlled by diafiltration. Emulsification and steady replacement of the aqueous phase were performed in parallel in a single-vessel setup. During the process, the solidification of the dispersed phase (drug:PLGA:solvent droplets) into microparticles was monitored with video-microscopy and focused beam reflectance measurement (FBRM) and the residual solvent content was analyzed with headspace gas chromatography (organic solvent) and coulometric Karl-Fischer titration (water).

Accelerated removal of solvent residuals from PLGA microparticles by alcohol vapor-assisted fluidized bed drying.

The removal of residual solvents from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by fluidized bed drying was investigated. Microparticles were prepared by the O/W solvent extraction/evaporation method and the influence of various process and formulation parameters on the secondary drying was studied. PLGA microparticles and films were characterized for residual organic solvent and water content, recrystallisation, surface morphology, drug loading and in-vitro release of the drugs dexamethasone and risperidone.

Acceleration of Final Residual Solvent Extraction From Poly(lactide-co-glycolide) Microparticles.

Purpose: The removal of the residual solvent dichloromethane from biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles was investigated by aqueous or alcoholic wet extraction or vacuum-drying.

Methods: Microparticles were prepared by the O/W solvent extraction/evaporation method. The solidified microparticles were separated by filtration and the effect of subsequent drying and wet extraction methods were investigated.

Porous PLGA microparticles prepared with nanosized/micronized sugar particles as porogens.

The objective of this study was to explore the use of nanosized/micronized sugar particles as porogens for preparing porous poly(lactide-co-glycolide) (PLGA) microparticles by a solid-in-oil-in-water (S/O/W) solvent evaporation method. Porous PLGA microparticles containing dexamethasone were prepared with different nanosized/micronized sugars (sucrose, trehalose and lactose), types of PLGA, and osmogens (NaCl or sucrose) in the external water phase. The microparticles were characterized for morphology, thermal properties, particle size, surface area, encapsulation efficiency and drug release/swelling during release.

Direct drug milling in organic PLGA solution facilitates the encapsulation of nanosized drug into PLGA microparticles.

The objective of this study was to prepare poly(lactide-co-glycolide) (PLGA) microparticles loaded with nanosized drug by combining non-aqueous wet bead milling and microencapsulation. 200-300 nm dexamethasone, hydrocortisone and dexamethasone sodium phosphate nanosuspensions were successfully prepared by wet bead milling the drug in dichloromethane using PLGA as a stabilizer. PLGA microparticles loaded with nanosized drugs were then prepared by a solid-in-oil-in-water (S/O/W) solvent evaporation method or solid-in-oil-in-oil (S/O/O) organic phase separation method.

A comparative study of PLGA microparticle properties loaded with micronized, nanosized or dissolved drug.

The objective of this study was to compare properties of poly(lactide-co-glycolide) (PLGA) microparticles loaded with dexamethasone or hydrocortisone in the micronized, nanosized or dissolved state. Dexamethasone and hydrocortisone were nanosized by wet bead milling. The microparticles were prepared by a solvent extraction/evaporation method and were characterized by particle size, encapsulation efficiency, drug solid-state, morphology, in vitro release and dynamic microparticle diameter changes during release.

Polymer type effect on PLGA-based microparticles preparation by solvent evaporation method with single emulsion system using focussed beam reflectance measurement.

Aim: This study aimed to investigate the effect of polymer type on solidification rate of PLGA polymeric microparticles and particle size/distribution of the emulsion droplets/hardened PLGA polymeric microparticles during solvent evaporation process using FBRM (Focussed Beam Reflectance Measurement).

Methods: PLGA polymeric microparticles were prepared by an O/W solvent evaporation method using various PLGA polymers, including PLGA Resomer® RG503H, RG502H and RG752H. The particle size mean, chord length distribution (CLD), and chord count of the emulsion droplets/hardened microparticles were monitored by FBRM.

Impact of dispersion time interval and particle size on release profiles of propranolol HCl and carbamazepines from microparticle blends system.

The objective of this study was to investigate the effect of dispersion time interval (DTI) on physicochemical properties of drug following the incorporation of propranolol HCl (Pro) and carbamazepine (CBZ) within ethyl cellulose (EC) microparticle blends using solvent evaporation method. The first Pro emulsion and second CBZ oil phase were dispersed in an external aqueous phase, with DTI of 0 and 60 min. The morphology of microparticle blends were characterized by SEM.

Incorporation of itraconazole nano-co-crystals into multiparticulate oral dosage forms.

Limited research has been performed on the downstream processing of nano-co-crystal suspensions into solid oral dosage forms. The objectives of this study were to evaluate the impact of three downstream processes (wet granulation, spray granulation and bead layering) on the performance of itraconazole-succinic acid (ITZ-SUC) nano-co-crystal suspension. An optimized ITZ-SUC nano-co-crystal suspension mixed with HPMC E5 was utilized for the downstream processing.

Combination of co-crystal and nanocrystal techniques to improve the solubility and dissolution rate of poorly soluble drugs.

Purpose: Solubility and dissolution rate are essential for the oral absorption and bioavailability of poorly soluble drugs. The aim of this study was to prepare nano-co-crystals by combination of nanocrystal and co-crystal technologies, and investigate its effect, in situ, on increased kinetic solubility and dissolution rate.

Methods: Co-crystals of itraconazole-fumaric acid, itraconazole-succinic acid, indomethacin-saccharin and indomethacin-nicotinamide were prepared and nano-sized by wet milling.

Kinetic solubility improvement and influence of polymers on controlled supersaturation of itraconazole-succinic acid nano-co-crystals.

Nano-co-crystals enhance the solubility and dissolution rate of poorly soluble drugs. The objective of this study was to obtain a better understanding of the dissolution process of nano-co-crystals and of the precipitation inhibition by various polymers. Itraconazole-succinic acid (ITZ-SUC) nano-co-crystal was chosen as model drug formulation to investigate the supersaturation and precipitation inhibition capabilities of various polymers (HPMC E5, HPMC E50, HPMCAS, HPC-SSL, PVPK30 and PVPVA64).

Real-time particle size analysis using focused beam reflectance measurement as a process analytical technology tool for continuous microencapsulation process.

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM). In this paper, we use FBRM measurements to investigate the effects of polymer type and compare the size distributions to those obtained using other sizing methods such as optical microscope and laser diffraction. FBRM was also utilized to measure the length-weighted chord length distribution (CLD) and particle size distribution (PSD) online during particle solidification, which could not be done with laser diffraction or nested sieve analysis.

Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness.

Purpose: The purpose of this study was to correlate the gel strength of swollen matrix tablets with their in vitro robustness against agitation intensity and applied mechanical forces. Five commercial products, i.e.

Data on the application of the focused beam reflectance measurement (FBRM): A process parameters dataset for the ethyl cellulose (EC) microparticles preparation by the solvent evaporation method.

The data article refers to the paper "Effect of solvent type on preparation of ethyl cellulose microparticles by solvent evaporation method with double emulsion system using focused beam reflectance measurement" [1]. Data presented here include the effect of solvent type, method of emulsification (an oil-in-water (O/W) or a water-in-oil-in-water (W/O/W)), external aqueous phase volume, stirring speed and ethyl cellulose concentration on the preparation of ethyl cellulose microparticles. Data also refer to the effect of above mentioned factors on the solidification rate, hardening time, particle size, particle size mean, chord length distribution (CLD) and chord count of microparticles.

Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy.

Nanocrystals represent an improvement over the traditional nanocarriers for dermal application, providing the advantages of 100% drug loading, a large surface area, increased adhesion, and the potential for hair follicle targeting. To investigate their advantage for drug delivery, compared to a base cream formulation, dexamethasone (Dx), a synthetic glucocorticoid frequently used for the treatment of inflammatory skin diseases, was covalently linked with the paramagnetic probe 3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) to DxPCA. To investigate the penetration efficiency between these two vehicles, electron paramagnetic resonance (EPR) spectroscopy was used, which allows the quantification of a spin-labeled drug in different skin layers and the monitoring of the drug release.

Quantification of porogen effect on the drug release from single- and multi-layered ethylcellulose coated pellets containing single or combined drugs.

The aim of this work was to develop a mathematical model to estimate the drug release from a conventional single-compartment reservoir pellet and extend its applicability to multi-compartment reservoir pellets. Conventional pellets were prepared by layering the drug onto starter-core then applying various ethylcellulose/HPC coatings for drug release control. Multi-layered pellets comprised a first drug layer of propranolol HCl (D) followed by a first controlled release coating (C) and consecutively a second drug layer of carbamazepine or caffeine (D) and then a second controlled-release coating (C).

Evaluation of manufacturing process parameters causing multilayer tablets delamination.

The aim of this study was to evaluate the influence of tableting process parameters, i.e. turret rotation speed, pre-compaction and main compaction pressures, and their interactions on layer adhesion of bilayer tablets.

Evaluation of Hydrogenated Soybean Phosphatidylcholine Matrices Prepared by Hot Melt Extrusion for Oral Controlled Delivery of Water-Soluble Drugs.

The aims of this study were to prepare hydrogenated soybean phosphatidylcholine (HSPC) matrices by hot melt extrusion and to evaluate resulting matrix potential to extend drug release in regard to drug loading and solubility for oral drug delivery of water-soluble drugs. The liquid crystalline nature of HSPC powder allowed its extrusion at 120°C, which was below its capillary melting point. Model drugs with a wide range of water solubilities (8, 20 and 240 mg/mL) and melting temperatures (160-270°C) were used.

pH-sensitive Eudragit® L 100 nanoparticles promote cutaneous penetration and drug release on the skin.

Nanoparticles (NPs) are promising carriers for dermal and transdermal drug delivery. However, the underlying dynamics of drug release from the NPs, especially, how the physiological changes of diseased skin influence the drug release, remain poorly understood. We utilized electron paramagnetic resonance (EPR) and confocal laser scanning microscopy (CLSM) to comprehensively investigate the penetration behavior of a spin-labeled dexamethasone (DxPCA)-loaded pH-sensitive Eudragit® L 100 NP on intact and barrier-disrupted skins.

Impact of change of matrix crystallinity and polymorphism on ovalbumin release from lipid-based implants.

The objectives of this study were to prepare lipid-based implants by hot melt extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate protein release to crystallinity and polymorphic changes of the lipid matrix. Two lipids, glycerol tristearate and hydrogenated palm oil, with different composition and degree of crystallinity were studied. Solid OVA was dispersed within the lipid matrixes, which preserved its stability during extrusion.

Preparation of amorphous indomethacin nanoparticles by aqueous wet bead milling and in situ measurement of their increased saturation solubility.

The aim of this study was to prepare amorphous indomethacin nanoparticles in aqueous media and to determine in situ their increased saturation solubility and dissolution rate. Drug nanosuspensions with a Z-average of ∼300 nm were prepared by wet media milling and afterwards freeze-dried. The drug solid state was analyzed by DSC, XRD and FTIR before and after the milling process.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings.

Saturated phosphatidylcholine as matrix former for oral extended release dosage forms.

The aim of this study was to evaluate the suitability of saturated phosphatidylcholine (Phospholipon® 90H) as extended release excipient in matrix tablets for three model drugs with different aqueous solubility (theophylline, caffeine and diprophylline). The tablets could be prepared by direct compression because of the favorable phospholipid powder flow properties (Carr's index: 12.64 and angle of repose: 28.

Protein Corona Formation on Colloidal Polymeric Nanoparticles and Polymeric Nanogels: Impact on Cellular Uptake, Toxicity, Immunogenicity, and Drug Release Properties.

The adsorption of biomolecules to the surface of nanoparticles (NPs) following administration into biological environments is widely recognized. In particular, the "protein corona" is well understood in terms of formation kinetics and impact upon the biological interactions of NPs. Its presence is an essential consideration in the design of therapeutic NPs.

Evaluation of a biphasic in vitro dissolution test for estimating the bioavailability of carbamazepine polymorphic forms.

The purpose of this study was to discriminate three crystal forms of carbamazepine (a BCS II drug) by in vitro dissolution testing and to correlate in vitro data with published in vivo data. A biphasic dissolution system (phosphate buffer pH6.8 and octanol) was used to evaluate the dissolution of the three polymorphic forms and to compare it with conventional single phase dissolution tests performed under sink and non-sink conditions.