Gelled emulsion particles for the controlled release of lipophilic volatiles during eating.

Gelled emulsion particles are discussed in relation to controlling the release of lipophilic volatiles in the mouth during eating, using a mass spectroscopic technique that enables real time measurement of volatiles on the breath. Our studies have demonstrated that by encapsulating triglyceride oil droplets within biopolymer gelled particles (70-5000 microm), the initial flavour release maxima were reduced by kinetically inhibiting the mass transfer of flavour through the particle. An important feature of this approach was that it was the oil droplets and not the volatiles that were encapsulated. Factors such as particle size, oil phase volume and the partition coefficient of the volatile all affected the rate of volatile release. To control the temporal release profile, gelled emulsion particles have been designed that break down in a controlled manner under physiological conditions in the mouth. The physiological 'trigger mechanisms' investigated included mechanical failure, melting and enzyme hydrolysis.     

Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.

Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion particle size and stability change with different oils. Cottonseed, linseed and evening primrose oils formed emulsions with very large and unstable particles. Squalene, light mineral oil and jojoba bean oil formed stable emulsions with small particles. The remaining natural oils formed moderately stable emulsions. Emulsions with smaller initial particle size were more stable than those with larger particles. The correlation between emulsion size made with different oils and two physical properties of the oils was also investigated. The o/w interfacial tension and particle size of the emulsion were inversely proportional. The effect of viscosity was less pronounced. To study how the oil component in the emulsion modulates the in vitro release characteristics of lipophilic drugs, three different emulsions loaded with two different drugs were prepared. Squalene, soybean oil and linseed oil emulsions represented the most, medium and the least stable systems, respectively. For the lipophilic drugs, release was the slowest from the most stable squalene emulsion, followed by soybean oil and then by linseed oil emulsions. Cationic emulsions were also prepared with the above three different oils as gene carriers. In vitro transfection activity was the highest for the most stable squalene emulsion followed by soybean oil and then by linseed oil emulsions. Even though the in vitro transfection activity of emulsions were lower than the liposome in the absence of serum, the activity of squalene emulsion, for instance, was ca. 30 times higher than that of liposome in the presence of 80% (v/v) serum. In conclusion, the choice of oil component in o/w emulsion is important in formulating emulsion-based drug or gene delivery systems.     

Plasma levels of diazepam in the dog and the rabbit after two different injection formulations, emulsion and solution

Diazepam is almost insoluble in water but can be dissolved in soya bean oil. If the oil phase is homogenized to a fine emulsion, a formulation of low toxicity is obtained, suitable for intravenous injection. Intramuscularly or subcutaneously, oily vehicles of drugs can be used to prolong the drug action. In the present study the plasma elimination of diazepam has been compared in the dog and the rabbit after intravenous administration of emulsion formulations or a solution in ethanolpropylene glycol. The result showed that the drug release from the lipid particles is rapid, as the plasma elimination pattern was equal to that of the solution. Furthermore, the same result was noted when emulsions were used where the lipid particle elimination from plasma was very slow or very rapid. The finely dispersed oil phase has a very large total contact surface with the plasma and this was supposed to explain the rapid drug diffusion. Because of the similar plasma curves the diazepam emulsion is suggested as a less toxic alternative to the conventional ethanol-propylene glycol solution.     

A multiplexed electrospray process for single-step synthesis of stabilized polymer particles for drug delivery

While conventional methods for biodegradable particle production rely predominately on batch, emulsion preparation methods, an alternative process based on multiplexed electrospray (ES) can offer distinct advantages. These include enhanced encapsulation efficiency of hydrophilic and hydrophobic agents, scale-up potential, tight control over particle size and excellent particulate reproducibility. Here we developed a well-controlled ES process to synthesize coated biodegradable polymer particles. We demonstrate this process with the Poly(DL-lactic-co-glycolic acid) system encapsulating amphiphilic agents such as doxorubicin (DOX), Rhodamine B (RHO_B) and Rhodamine B octadecyl ester perchlorate (RHO_BOEP). We show that in a single-step flow process particles can be made encapsulating the agent with high efficiency and coated either with emulsifiers that stabilize them in solution or that may facilitate further functionalization for targeted drug delivery. The coating process allows for the surface modification of the particles without further changes in particle size or morphology, and with minimal loss of drug (> 94% encapsulation efficiency). This synthesis technique is well suited for massive scale-up using microfabricated, multiplexed arrays consisting of multiple electrospray nozzles operating in parallel. A simple analytical model of the diffusion of the encapsulated agent within the polymer reveals two distinct phases in the cumulative release profile: a first phase in which the release is dominated by diffusion and a second phase with a slower release related to the erosion of the polymer matrix. The first, diffusion-driven stage is highly affected by particle agglomeration properties, whereas the second one shows a much less pronounced dependence on particle size. Modeling suggests that the size of the particles will substantially influence the initial burst in both the percentage of drug released and the rate at which it is released. It will also affect to a smaller extent the secondary slow and sustained release. Our study highlights the importance of tight control over particle size and morphology and the avoidance of particle aggregation for control over the release kinetics and formulation repeatability.     

Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles.

The objective of the study was to investigate the effect of particle size of nano- and microparticles formulated from poly(D,L-lactide-co-glycolide) (50:50 PLGA) on polymer degradation and protein release. Since the surface area to volume ratio is inversely proportional to the particle size, it is hypothesized that the particle size would influence the polymer degradation as well as the release of the encapsulated protein. PLGA nano- and microparticles of approximate mean diameters of 0.1, 1 and 10 microm, containing bovine serum albumin as a model protein, were formulated using a multiple water-in-oil-in-water emulsion solvent evaporation technique. These particles were incubated at 37 degrees C in phosphate-buffered saline (pH 7.4, 154 mM) and the particles were characterized at various time points for molecular weight of polymer, surface-associated polyvinyl alcohol content (PVA), and the particle surface topology using scanning electron microscopy. The supernatants from the above study were analyzed for the released protein and PVA content. Polymer degradation was found to be biphasic in both nano- and microparticles, with an initial rapid degradation for 20-30 days followed by a slower degradation phase. The 0.1 microm diameter nanoparticles demonstrated relatively higher polymer degradation rate (P<0.05) during the initial phase as compared to the larger size microparticles (first order degradation rate constants of 0.028 day(-1), 0.011 day(-1) and 0.018 day(-1) for 0.1, 1 and 10 microm particles, respectively), however the degradation rates were almost similar (0.008 to 0.009 day(-1)) for all size particles during the later phase. All size particles maintained their structural integrity during the initial degradation phase; however, this was followed by pore formation, deformation and fusion of particles during the slow degradation phase. Protein release from 0.1 and 1 microm particles was greater than that from 10 microm size particles. In conclusion, the polymer degradation rates in vitro were not substantially different for different size particles despite a 10- and 100-fold greater surface area to volume ratio for 0.1 microm size nanoparticles as compared to 1 and 10 microm size microparticles, respectively. Relatively higher amounts of the surface-associated PVA found in the smaller-size nanoparticles (0.1 microm) as compared to the larger-size microparticles could explain some of the observed degradation results with different size particles.     

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 2. Modulation of release rate.

Amphiphilic multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were used as matrix material for protein-loaded microspheres. The efficiency of lysozyme entrapment by a double emulsion method was found to depend on the swelling behavior of the polymers in water and decreased from 100% for polymers with a degree of swelling of less than 1.8 to 11% for PEG-PBT copolymers with a degree of swelling of 3.6. The particle size could be controlled by varying the concentration of the polymer solution used in the microsphere preparation. An increase in the polymer concentration resulted in a proportional increase in the particle size. The in vitro release profiles of the encapsulated model protein lysozyme could be precisely tailored by variation of the copolymer composition and the size of the microspheres. Both a slow continuous release of lysozyme, and a fast release which was completed within a few days could be obtained. The release behavior, attributed to a combination of diffusion and polymer degradation, could be described by a previously developed model.     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景:如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。目的:研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。方法:采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。结果与结论:所制微球治疗剂光滑圆整,大小均一,平均粒径(154.42±26.76)nm,载药率(16.5±1.45)%,包封率(87.84±4.79)%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景：如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。目的：研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。方法：采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。结果与结论：所制微球治疗剂光滑圆整,大小均一,平均粒径（154.42±26.76）nm,载药率（16.5±1.45）%,包封率（87.84±4.79）%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

Physically bonded nanoparticle networks: a novel drug delivery system.

Monodispersed nanoparticles consisting of interpenetrating polymer networks (IPNs) of polyacrylic acid (PAAc) and poly(N-isopropylacrylamide) (PNIPAM) were prepared by a seed-and-feed method. The temperature-dependent viscosity measurement revealed that the IPN nanoparticle dispersions with polymer concentrations above 2.5 wt.% underwent an inverse thermoreversible gelation at about 33 degrees C. Dextran markers of various molecular weights as model macromolecular drugs were mixed with the IPN nanoparticle dispersion at room temperature. At body temperature, the dispersion became a gel. The drug release profiles were then measured using UV-Visible spectroscopy as a function of particle size and polymer concentration. The schematic structure of the nanoparticle network was proposed based on the experimental results. The drug delivery model presented here was significant because such a dispersion and a drug was mixed without chemical reaction at room temperature to form a drug delivery liquid. This liquid could be injected into a body to form in situ a gelled drug depot to release the drug slowly.     

Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugs.

This study investigates the submicron lipid emulsion as a potential parenteral drug delivery system for nalbuphine and its ester prodrugs. Submicron emulsions were prepared using egg phospholipid as the main emulsifier, various co-emulsifiers were also incorporated, including Brij 30, Brij 98, and stearylamine. Squalene as the oil phase formed stable emulsions with small particles. Drug release was affected by incorporating various co-emulsifiers and drugs with various lipophilicity. The loading of nalbuphine into lipid emulsions resulted in the slower and sustained release of nalbuphine. Lipid emulsions containing Brij 98 could further enhance the release of prodrugs as compared to the aqueous solution (control) especially for nalbuphine enanthate (NAE). Hemolysis caused by the interaction between erythrocytes and lipid emulsions was investigated. Brij 30 and Brij 98 could shield the hemolytic activity of phospholipids in the oil/water interface, decreasing the acute toxicological potential of the emulsions. The in vivo analgesic activity of various emulsions was examined by a cold ethanol tail-flick test. The analgesic duration and potency were significantly increased by incorporating nalbuphine and NAE into Brij 98-containing emulsions. There was no need for nalbuphine benzoate (NAB) to show a controlled delivery manner by encapsulating into emulsions, since NAB itself could prolong the analgesic duration of nalbuphine due to the slow enzyme degradation. The in vivo analgesic activity correlated well to the profiles of in vivo pharmacokinetic profiles. The study demonstrates the feasibility of using submicron lipid emulsion as the parenteral drug delivery system for nalbuphine and its prodrugs.     

Microparticle formation and its mechanism in single and double emulsion solvent evaporation.

The emulsification is the first step of the emulsification solvent evaporation method and has been extensively investigated. On the contrary the second step, the solvent transport out from the emulsion droplets that determine the particle morphology and with great influence on the microparticles encapsulation and release behavior has been scarcely studied. This study investigates the mechanism of the solvent elimination from the emulsion droplets and its influence on the particle morphology, encapsulation and release behavior. Usually, the solvent is highly volatile that makes the solvent elimination process very fast thus difficult to observe. In order to observe in detail the microparticle formation, the initial emulsion was monitored by optical microscope under controlled solvent evaporation conditions. The results from the optical microscopic observations corroborated with laser diffractometry analysis showed that in single emulsion formulations, spherical microparticles are formed by accelerated solvent elimination due to the combined effects of high solvent volatility and polymer precipitation. The solvent expulsion accompanied by important shrinkage generates on the microparticle surface a thin layer of nanoparticles attested by scanning electron microscopy and laser diffractometry. During the intense solvent elimination, the encapsulated substance is drained, affecting the loading efficiency. Furthermore, it will concentrate towards the microparticle surface contributing to the initial burst release. In double emulsion formulations, microparticles with different morphologies are generated due to the presence of the aqueous-phase microdroplets inside the emulsion droplet. During the solvent elimination, these microdroplets generally coalesce under the pressure of the precipitating polymer. Depending mainly on the polymer concentration and emulsification energies, the final microparticles will be a mixture of honeycomb, capsule or plain structure. During the shrinkage due to the incompressibility of the inner microdroplets, the precipitating polymer wall around them may break forming holes through which the encapsulated substance is partly expulsed. Through these holes, the encapsulated substance is further partitioning with the external aqueous phase during solvent evaporation and contributes to the initial burst release during the application.     

Preparing polymer-based sustained-release systems without exposing proteins to water–oil or water–air interfaces and cross-linking reagents

We report a method to load proteins into polymer-based sustained-release systems without exposing them to water–oil or water–air interfaces, factors known to denature proteins. By dispersing a dextan solution containing a protein into a PEG solution containing small amount of alginate, a stable aqueous–aqueous “emulsion” was formed. The poly-anionic alginate generated a diffuse double layer around each dextran droplet to prevent them from contacting with each other and fusing to a block phase. Proteins distributed in the stabilized dextran droplets by preferential partition favoring dextran. Freeze-drying this emulsion resulted in protein-loaded dextran particles, 1–2 µm in diameter and 1.6 g/cm³ in density. The particles were harvested by washing the lyophilized powder using organic solvents to remove the PEG continuous phase. An activity assay of encapsulated β-galactosidase indicated that protein activity was preserved during the particle-forming process including the step of sonicating the particles in organic solvents. The dextran particles also improved release profile and integrity of proteins when encapsulated in degradable polymer sustained-release systems. The aqueous–aqueous emulsion offers a convenient way to prepare solvent-resistant protein–polysaccharide particles that can easily be incorporated in a variety of polymer-based pharmaceutical dosage forms and medical devices such as microspheres, scaffolds and drug-eluting stents for sustained-release protein delivery.     

Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions.

In this study, anomalous dissolution behaviour of tablets consisting of sugar glass dispersions was investigated. The poorly aqueous soluble diazepam was used as a lipophilic model drug. The release of diazepam and sugar carrier was determined to study the mechanisms governing dissolution behaviour. The effect of carrier dissolution rate and drug load was tested with four different sugars, in the order of decreasing dissolution rates: sucrose, trehalose and two oligo-fructoses; inulinDP11 and inulinDP23 having a number average degree of polymerization (DP) of 11 and 23, respectively. Diazepam was incorporated in these sugar glasses in the amorphous state by means of freeze drying using water and tertiary butyl alcohol (TBA) as solvents. None of the tablets disintegrated during dissolution. Dissolution of 80% of the lipophilic drug within 20 min was found when diazepam and sugar dissolution profiles coincided. The sugar carrier and diazepam dissolved at the same rate, which was constant in time and fast. This condition was met for relatively slow dissolving carriers like the inulins or for low drug loads. For relatively fast dissolving carriers like sucrose or trehalose with high drug loads, release profiles of diazepam and sugar did not coincide: diazepam dissolved much more slowly than the sugars. In case of non-coinciding release profiles, diazepam release was split into three phases. During the first phase non-steady-state dissolution was observed: diazepam release accelerated and a drug rich layer consisting of crystalline diazepam was gradually formed. This first phase determined the further release of diazepam. During the second phase a steady-state release rate was reached: zero-order release was observed for both drug and carrier. During this phase, the remaining (non-crystallised) solid dispersion is dissolved without the further occurrence of crystallisation. The third phase, starting when all carrier is dissolved, involved the very slow dissolution of crystallised diazepam, which was present either as the skeleton of a tablet resulting in a zero-order release profile or as separate particles dispersed in the dissolution medium resulting in a first-order release. To understand the anomalous dissolution behaviour, a model is proposed. It describes the phenomena during dissolution of amorphous solid dispersion tablets and explains that fast dissolution is observed for low drug loads or slow dissolving carriers like inulin.     

Influence of the co-encapsulation of different non-ionic surfactants on the properties of PLGA insulin-loaded microspheres.

The aim of this work was to produce insulin-loaded microspheres allowing the preservation of peptide stability during both particle processing and insulin release. Our strategy was to combine the concepts of using surfactants to improve insulin stability while optimising overall microsphere characteristics such as size, morphology, peptide loading and release. Bovine insulin was encapsulated within poly(lactide-co-glycolide) (PLGA 50:50, Resomer RG504H) microspheres by the multiple emulsion-solvent evaporation technique. Microspheres were prepared by adding to the primary emulsion three non-ionic surfactants, poloxamer 188, polysorbate 20 and sorbitan monooleate 80, at different concentrations (1.5 and 3. 0% w/v). The presence of surfactants was found to decrease the mean diameter and to affect the morphology of the microspheres. Insulin encapsulation efficiency was reduced in the presence of surfactants and especially for sorbitan monooleate 80, in a concentration-dependent mode. The influence of the surfactants on the interactions between insulin and PLGA together with the primary emulsion stability were found to be the major determinants of insulin encapsulation. The release of insulin from microspheres was biphasic, showing an initial burst effect followed by a near zero-order release for all the batches prepared. The initial burst was related to the presence of insulin molecules located onto or near to the microsphere surface. In the presence of surfactants, a faster insulin release with respect to microspheres encapsulating insulin alone was observed. Insulin stability within microspheres after processing, storage and release was evaluated by reversed phase- and size-exclusion-HPLC. The analysis of microsphere content after processing and 6 months of storage showed that insulin did not undergo any chemical modification within microspheres. On the contrary, during the period of sustained release insulin was transformed in a high-molecular weight product, the amount of which was related to the surfactant used. In conclusion, polysorbate 20 at 3% w/v concentration was the most effective in giving regular shaped particles with both good insulin loading and slow release, and limiting insulin modification within microspheres.     

Unimodal sized silica nanocapsules produced through water-in-oil emulsions prepared by sequential irradiation of kilo- and submega-hertz ultrasounds

This study investigates the regulation of the size of 100 nm hollow-sphere silica particles using surfactant-free water-in-oil (W/O) emulsion. First, water droplets were dispersed in soybean oil via sequential ultrasound irradiation (28 kHz → 200 kHz → 950 kHz). A precursor of hollow silica particles was prepared using hydrolysis and polymerization of methylsilyl trichloride into a stable W/O emulsion. The final structure/morphology of the silica particles was influenced by the volume ratio of water/soybean oil, the cycle number of the sequential ultrasound irradiation, and the amount of organosilane added to the emulsion. The emulsion was stabilized by Ostwald ripening, as the size distribution at 5/10³ (water/oil = v/v) was a bimodal split between a water droplet size of a few μm and some with a size of a few tens of nm. The most appropriate cycle number was 3 in this system. Further cycling to 5 resulted in a broad and bimodal size distribution of the final particles due to rapid coalescence of water droplets. Subsequent hydrolysis of methylsilyl trichloride consumed water with diminishing large droplets, forming fine and unimodal (0.12 ± 0.02 μm) hollow silica particles. Very fine and uniform-sized hollow particles (0.08 ± 0.01 μm) were successfully produced by decreasing the volume ratio to 1/10³ (water/oil) because of a transparent stable emulsion as a homogeneous template of the hollow structures.

Silica nanocapsules were prepared using water droplets dispersed in soybean oil via sequential ultrasound irradiation (28 kHz → 200 kHz → 950 kHz).     

Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions.

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of approximately 80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.     

The design and evaluation of a novel targeted drug delivery system using cationic emulsion-antibody conjugates.

In an attempt to design a targeted drug delivery system to tumors' over-expressing H-ferritin specifically recognized by a monoclonal antibody, AMB8LK, a cationic emulsion - AMB8LK conjugate was prepared. A novel cross-linker molecule bearing maleimide group was synthesized and added to cationic emulsion formulation for AMB8LK Fab' fragment covalent coupling. NMR spectroscopy confirmed the cross-linker synthesis and the preservation of the active maleimide function. SDS gel-electrophoresis results corroborated the formation of the Fab' fragment. Different densities of Fab' fragments (10-200 Fab'/oil droplet) were conjugated to emulsion droplet interface and no changes in the physico-chemical properties were observed ( approximately 120 nm size and zeta potential of approximately +30 mV). The coupling efficiency ranged from 55% to 70% and was visualized by TEM showing gold particles attached to the droplet interface. Cell culture studies demonstrated specific binding to cells as confirmed by the occurrence of the marked reduction in binding when free AMB8LK Mab was incubated before adding the AMB8LK-emulsion conjugate to the cells. The coupling of AMB8LK Fab' fragment to the cationic emulsion increased the cells uptake by 50% as compared to non-conjugated respective cationic emulsion. Appropriate conditions were, thus, identified for coupling AMB8LK Fab' fragment to cationic emulsion without altering the specificity and affinity of the Mab fragment to the tumor antigen.     

pH compartmented w/o/w multiple emulsion: a diffusion study.

In order to develop w/o/w emulsions characterized by two separate aqueous phases of different pH, a preliminary study was carried out to obtain a better insight into the possible diffusion processes taking place between an inner acidic aqueous phase and an external phase of higher pH (pH approximately 6). In fact, such systems could be of great interest for pharmaceutical use. For this purpose, a model emulsion was formulated. The study of pH and conductivity showed that acidic species transport take place between the two aqueous compartments. The three main release mechanisms that might be responsible for this passage across the oil phase were investigated: breakdown of oil globules, facilitated transport by surfactant micelles across the oil phase or by Fickian diffusion. It appears that this last mechanism was involved. In order to control this diffusion process, an alkaline species, octadecylamine was introduced in the oil phase. This compound could form an ion pair with the lactate ion at the interface of the external aqueous phase and the oil phase, thus, limiting the acidification of the external aqueous phase.     

Recent progress in Pickering emulsions stabilised by bioderived particles

In recent years, the demand for non-surfactant based Pickering emulsions in many industrial applications has grown significantly because of the option to select biodegradable and sustainable materials with low toxicity as emulsion stabilisers. Usually, emulsions are a dispersion system, where synthetic surfactants or macromolecules stabilise two immiscible phases (typically water and oil phases) to prevent coalescence. However, synthetic surfactants are not always a suitable choice in some applications, especially in pharmaceuticals, food and cosmetics, due to toxicity and lack of compatibility and biodegradability. Therefore, this review reports recent literature (2018–2021) on the use of comparatively safer biodegradable polysaccharide particles, proteins, lipids and combinations of these species in various Pickering emulsion formulations. Also, an overview of the various tuneable factors associated with the functionalisation or surface modification of these solid particles, that govern the stability of the Pickering emulsions is provided.

In a Pickering emulsion, solid particles accumulate at the interface between two immiscible phases to reduce coalescence by forming a physical barrier. Using bioderived particles is becoming popular to generate more sustainable Pickering emulsions.     

Mechanistic aspects of the release of levamisole hydrochloride from biodegradable polymers.

The release of levamisole hydrochloride from poly-DL-lactide-co-glycolide compacts prepared at 5, 10 and 20% drug loading using two different particle size fractions of drug (90-125 and 125-250 microm) was investigated. Release profiles were significantly different from those previously reported for compacts prepared using the base form of the drug. Release was found to occur in a biphasic manner, with an initial fast release phase followed by a slower polymer degradation controlled release phase. The drug release profiles were successfully described by a model combining contributions from a first-order initial release phase and a polymer degradation controlled drug release phase. The fraction of drug released in the initial burst phase (F(B)) was attributed to the dissolution of drug domains situated at the surface of the polymer-drug compact and this fraction tended to increase with increasing drug particle size, as expected from the model. The increase in F(B) with increased loading was attributed to the clumping of dispersed drug particles which effectively increased the proportion of drug linked to the compact surface.