Increased Saturation Solubility Research Articles

Pharmaceutical Nanoparticles Formation and Their Physico-Chemical and Biomedical Properties.

The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows the therapeutic effectiveness of pharmaceutical preparations to be increased due to several factors: (1) the high specific surface area of nanomaterials, and (2) the high concentration of surface-active centers interacting with biological objects. In the case of drug nanoforms, even low concentrations of a bioactive substance can have a significant therapeutic effect on living organisms. These effects allow pharmacists to use lower doses of active components, consequently lowering the toxic side effects of pharmaceutical nanoform preparations. It is known that many drug substances that are currently in development are poorly soluble in water, so they have insufficient bioavailability. Converting them into nanoforms will increase their rate of dissolution, and the increased saturation solubility of drug nanocrystals also makes a significant contribution to their high therapeutic efficiency. Some physical and chemical methods can contribute to the formation of both pure drug nanoparticles and their ligand or of polymer-covered nanoforms, which are characterized by higher stability. This review describes the most commonly used methods for the preparation of nanoforms (nanoparticles) of different medicinal substances, paying close attention to modern supercritical and cryogenic technologies and the advantages and disadvantages of the described methods and techniques; moreover, the improvements in the physico-chemical and biomedical properties of the obtained medicinal nanoforms are also discussed.

Formulation, Development, and Evaluation of Bosentan Monohydrate Spray Dried- Solid Dispersion Tablets for Improved Dissolution Profile

Bosentan monohydrate (BM) is utilized for the treatment of pulmonary arterial hypertension, exhibiting poor aqueous solubility and bioavailability. This study aims to enhance the dissolution rate of the drug using Eudragit®EPO through spray drying. The drug and Eudragit®EPO were combined in ratios of 1:1, 1:2, 1:3, 1:4, and 1:5 (w/w) to generate compositions SD1 to SD5. SD5, at a 1:5 drug-to-carrier ratio, demonstrated a statistically significant increase in saturation solubility and drug content. Six tablet formulations (F1 to F6) containing SD5 and tableting excipients were developed and processed. Formulation F2, consisting of 26.36% HPMC K4M and 23.63% MCC, exhibited the highest dissolution and drug release. The probable mechanism underlying BM dissolution in SD involves its amorphous form and the solubilizing effect facilitated by hydrogen bonding between BM and Eudragit®EPO. The carrier's binding effect likely contributed to high tensile strength, low friability, and extended disintegration time. Direct mixing of SD with HPMC might have improved the uniformity of SD within the tablet matrix and the release profile. This study demonstrates the efficacy of spray drying in preparing SD of BM with Eudragit®EPO, potentially enhancing its solubility and stability.

Carvedilol solubility enhancement by multicomponent crystallization with coformers of benzoic acid, isonicotinamide, and saccharin

Multicomponent crystallization is a method that can modify the physicochemical properties of Carvedilol (CVD), thereby increasing its solubility. Based on in silico screening the coformers (Benzoic Acid, Isonicotinamide, and Saccharin) showed non-covalent interactions with CVD, so the multicomponent crystal preparation of CVD by solvent evaporation method used these coformers with mole ratios of 1:1, 1:2, and 2:1. Multicomponent CVD:Isonicotinamide (1:2) exhibits increased saturation solubility of up to 140 mg/L and increased dissolution of up to 99.48%. The infra-red (IR) spectrum showed a peak shift, a thermogram pattern that was different from the DSC results, and a new peak on the XRD multicomponent crystal diffractogram indicating the formation of a new solid phase compared to pure Carvedilol. Therefore, the formation of multicomponent crystals can increase the solubility and dissolution rate of CVD, and all characteristics indicate the presence of interaction between CVD and Isonicotinamide, and the formation of a new solid phase.

엔잘루타마이드의 용해도 개선을 위한 고형의 자가나노유화 약물전달시스템

The objective of this study was to develop a novel enzalutamide-loaded solidified self-nanoemulsifying drug delivery system formulation with enhanced solubility and dissolution rate. Various oil and surfactant were screened, then Medium Chain Triglyceride oil and Polysorbate 80 and Labrafil M2125CS were selected as oil and a surfactant. Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, SNEDDS consisted of MCT oil (oil), Polysorbate 80 (surfactant) and Labrafil M2125CS (co-surfactant) at a weight ratio of 20:70:10. The SNEDDS produced the emulsion droplet size 18.66±0.88 nm. Spray drying technique was used to convert the selected enzalutamide-loaded SNEDDS into solid SNEDDS with inert carrier such as silicon dioxide. Enzlautamide-loaded solid SNEDDS was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffractometry, dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 15.37±0.49 nm and there was no change in particle size between with or without drug. SEM and PXRD results suggested that enzalutamide existed in amorphous form in enzalutamide-loaded solid SNEDDS. In addition, enzalutamide-loaded solid SNEDDS increased saturation solubility 42-fold and dissolution rates 23- fold compared to crystalline enzalutamide. Therefore, the solid SNEDDS could be a potential nano-sized drug delivery system for poorly water-soluble drug enzalutamide.

Preparation of Posaconazole Nanosponges for Improved Topical Delivery System

The objective of the current research was to develop the posaconazole (PCZ) loaded NS into the carbopol 934 polymeric gel for prolonged drug release and improved topical delivery; seven different nanosponge formulations of PCZ were formulated using the emulsion solvent diffusion method using various amounts of polymer (ethylcellulose, EC). The aqueous and dispersed phases were prepared using polyvinyl alcohol (PVA) and dichloromethane. The prepared nanosponges (NS) were studied for particle size, structural appearance, and in vitro drug release. Furthermore, the selected formula was formulated as hydrogel and was evaluated for physical characteristics, drug content, and in-vitro drug release. Morphological studies revealed irregular shapes, rough and porous surfaces of nanosponges. The particle sizes were in the range of 201.6 ± 29.9 to 4904.7 ± 540.4 nm. In-vitro release studies revealed the sustained release pattern of the drug-loaded nanosponges. The lyophilized PCZ-NS formula had a 12-fold increase in saturation solubility over PCZ pure powder. Fourier transform infrared spectroscopy (FTIR) of the selected formula showed no significant shifts in the positions of wavenumbers compared to that of pure drug. This indicates there is no interaction between drug and excipients used. PCZ NS loaded hydrogel significantly improved the dissolution rate, which was significantly higher (p is less than 0.05) than that of pure PCZ hydrogel.

Stability Testing of Amoxicillin Nano-suspension as Promising Tool for Drug Delivery System

While nano-suspension amoxicillin is one of the approaches for improving dissolution rate of amoxicillinan antibiotic used widely. Stabilizing these nanodosage forms is always a challenge. The present study utilizes nanoprecipitation solvent evaporation technique for preparation of amoxicillin nanoparticles andproposed stability study approach of the same. The methodology was based on investigating stability of amoxicillin nano suspension in vitro, the optimized drug(polymer ratio re-formulated into nano-suspensions) and we compared our results with marketed suspensions. Samples were initially characterized and then subjected to stability testing at ambient temperature and relative humidity up to 6 months assayed using a validated HPLC method. During initial characterization, increase in saturation solubility and dissolution rate observed in all samples. During stability testing, there was gradual decrease in saturation solubility and dissolution rate of the samples, over the period of 3 months. This study considers long-term isothermal measurements, consistent with short-term non-isothermal (accelerating) measurements, providing predictive model to calculate the isothermal degradation periods. As per our results, we agree with the possibility to calculate the value of kinetic constants based on a fixed degradation limit, regardless of the shape of the curve. The accuracy of the prediction would be assessed by comparison of estimated shelf life versus data coming from traditional stability studies.

Review on nanoparticles technology and applications based on drug delivery

This review is about nanocrystal technology and applications of nanocrystals based on drug delivery. Nanocrystal technology is applied to the drug molecules to access for good drug delivery as nano dimensioned carrier. Nanoparticle has at least one dimension smaller than 100 nanometers. The major properties of nanoparticles are increases dissolution velocity by surface area enlargement and increase in saturation solubility. Nanoparticle’s productions are done with different methods such as precipitation method, Milling method, and homogenized method. Nanoparticles has got wide range of applications based on drug delivery such as gastrointestinal tract, brain, tumor cell targeting, respiratory tract, and gene delivery.

Development and Characterization of Venetoclax Nanocrystals for Oral Bioavailability Enhancement.

Venetoclax (VX) used in the treatment of chronic lymphocytic leukemia possesses low oral bioavailability (5.4%) and undergoes first-pass metabolism. Development of a formulation to overcome its bioavailability problem can be done by using nanocrystals which has many scientific applications. Nanocrystals of VX were formulated using amalgamation of precipitation and high-pressure homogenization method, in which polyvinyl alcohol (PVA) was selected as stabilizer. Process parameters like concentration of stabilizer, homogenization pressure, number of homogenization cycle, and concentration of lyoprotectant were optimized to obtain the desired particle size for the preparation of nanocrystal formulation. HPLC methods were developed and validated in-house for determination of in vitro dissolution data and in vivo bioavailability data. Physicochemical characterization was done to determine the particle size (zeta sizer), crystalline nature (DSC and XRPD), solubility (shaker bath), and dissolution (USP type 2 apparatus). Lyophilized VX nanocrystals of size less than 350 nm showed substantial increase in saturation solubility (~20 folds) and dissolution in comparison with free VX. In vitro release study revealed that 100% dissolution was achieved in 120 min as compared to VX free base which is having less than 43.5% dissolution in 120 min. Formulations of VX remain stable for 6 months under accelerated stability conditions. In vivo pharmacokinetic data in male Sprague-Dawley rats showed (~2.02 folds) significant increase in oral bioavailability of VX formulation as compared to free drug because of rapid dissolution and absorption which makes the nanocrystal formulation a better approach for oral administration of poorly soluble drugs.

Novel nanocrystal-based formulations of apremilast for improved topical delivery.

Nanocrystals can enhance skin penetration of drug by increased saturation solubility, dissolution rate and adhesion on the skin. Apremilast is 'difficult-to-deliver' in viable layers (epidermis, dermis) and stratum corneum (SC) owing to its poor aqueous solubility and modest lipophilicity, respectively. Apremilast is currently available as oral tablet formulation for the indication of psoriasis but its effectiveness is limited by systemic side effects. Therefore, the present study aimed to develop novel nanocrystal-based formulations of apremilast for improved topical delivery. Nanosuspension was prepared using wet media milling and exhibited a mean particle size of 200nm. The saturation solubility of nanocrystals was improved by 2-fold than micronized apremilast and showed significant advantage during dissolution study. Nanosuspension and micronized apremilast was incorporated into gel and cream and characterized for rheological properties. Skin permeation and ex vivo dermatokinetic study of topical formulations were performed on pig ear skin at a dose of 1% w/w using Franz diffusion cells. Skin permeation studies indicated that non-detectable amount of apremilast permeated through pig ear skin during exposure of formulations. Nanosuspension showed 2.6- and 3.2-fold drug penetration in SC and viable layers, respectively, over microsuspension. Nanogel showed 2.7- and 2.4-fold drug penetration in SC and viable layers, respectively, over microgel. Nanocream showed 1.2- and 2.8-fold drug penetration in SC and viable layers, respectively, over microcream. Thus, nanocrystal-based formulations of apremilast aid in selective delivery into viable layers by crossing the SC barrier. This is of paramount importance in enhancing therapeutic effectiveness utilizing localized delivery and provides an alternative delivery approach for the treatment of psoriasis. Graphical abstract.

Symurban Nanocrystals for Advanced Anti-Pollution Skincare

Several of most common dermatoses worldwide, e.g., psoriasis and atopic dermatitis, are worsened in their clinical picture when the skin is regularly exposed to an increased air pollution level, e.g., particulate matter. This is explainable by the activation of the aryl hydrocarbon receptor (AhR) in the skin, which results in an increased release of proinflammatory cytokines and matrix metalloproteinases. Symurban is a competitive AhR antagonist and thus allows the effective protection of skin. In order to improve its dermal bioavailability as a poorly soluble active agent (0.25 µg/mL), nanocrystals were prepared and evaluated. Nanocrystals are pure active crystals reduced in particle size to the submicron range of 100 to 1000 nm. They feature the properties of nanocrystals, such as increased saturation solubility and dissolution velocity, without having to be declared as nanomaterial. Production methods and parameters were systematically investigated. Wet bead milling at 2000 rpm for 30 min yielded the best results. A z-average of 280 nm was achieved for a 10% Symurban suspension with a polydispersity index of 0.20, indicating a narrow size distribution. For the long-term stabilization of the nanocrystal suspension, the performance of 15 surfactants of different categories and HLB values were investigated and evaluated. It was found that non-ionic surfactants in general were better able to stabilize the system than anionic or amphoteric surfactants. Highest stability of over 12 months at 25 °C was achieved with 2% Plantacare 810 UP, an ECOCERT surfactant with high skin tolerance. The suspension was also chemically long-term stable with >97% of remaining Symurban over 12 months. The saturation solubility of Symurban as nanocrystals was significantly increased from 0.25 to 2.9 μg/mL, which corresponds to a factor of >11. In a case study of one male volunteer with healthy skin conditions, penetration profiles of Symurban nanocrystal hydrogel and commercial anti-pollution serum containing an identical amount of Symurban were determined and compared. After 20 min of exposure, the relative Symurban concentration in the deeper skin layers (tape 19-30) was more than two times higher for nanocrystal hydrogel (16%) than the commercial serum (7%). These results suggest that nanocrystals are a promising delivery system for the poorly soluble anti-pollution agent Symurban.

Effects of Different Formulation Methods on Drug Crystallinity, Drug-Carrier Interaction, and Ex Vivo Permeation of a Ternary Solid Dispersion Containing Nisoldipine

Solid dispersion (SD) is an established approach to increase the solubility and dissolution of BCS class II drugs. The selection of a suitable method of preparation and the suitable polymeric carrier are the two most important parameters for a successful SD. The present research is aimed to evaluate the effect of preparation method on drug crystallinity, drug-polymer interaction, ex vivo permeability, and SD stability. A ternary SD containing nisoldipine as drug and PVP K30, poloxamer 188 as the carrier was prepared by hot melt mixing, solvent evaporation by rotary vacuum evaporator, and lyophilization. The prepared samples were analyzed in comparison in order to meet the objectives. All three methods yielded a mixed system of the crystalline and amorphous phase with a significant increase in saturation solubility compared to the raw drug. Infra-red spectroscopy study showed the highest degree of H bonding between drug and carrier in the freeze-dried formulation. X-ray diffraction study showed maximum loss of drug crystallinity from the rotary vacuum evaporated SD (3.70% at 11.3, 2θ angle). Ex vivo permeability study showed the maximum drug permeation by freeze-dried product. But freeze-dried product was shown to be the least stable in stability analysis. In terms of product stability, melt mixing is the best out of the three methods tested. Different methods of preparation have different impacts on functional group interaction, loss of crystallinity, ex vivo permeation, and stability of ternary SD.

High‐gravity‐assisted synthesis of aqueous nanodispersions of organic fluorescent dyes for counterfeit labeling

AbstractOrganic fluorescent dyes have attracted wide interest because of their high photoluminescence quantum efficiencies. However, there are several application limitations arising from their hydrophobicity, poor dispersity and large particle sizes. These problems can be improved by preparing nanoparticles with a small size. Herein, we present a continuous approach to efficiently prepare an aqueous nanodispersion of water‐insoluble organic fluorescent dye Nile red (NR) with monodispersed and uniform nanoparticles (35 nm) by high‐gravity antisolvent precipitation in a rotating packed bed (RPB). In contrast, NR nanodispersions prepared using a traditional batch stirred tank (ST) had a broad size distribution (20–150 nm). Due to its small size effect and good dispersity in water, the RPB nanodispersion displayed significantly increased saturation solubility and much stronger fluorescent intensity compared to raw NR, and was obviously superior to the ST counterpart. Furthermore, NR nanodispersions were mixed with ink to draw fluorescent patterns on paper for counterfeit labeling.

SmartPearls® for dermal bioavailability enhancement – Long-term stabilization of suspensions by viscoelasticity

smartPearls® are a novel dermal delivery system based on mesoporous (pores 2–50 nm) particles, developed in 2014. Their pores can be loaded with active which is long-term stabilized in its amorphous state. The increased saturation solubility by the amorphous state leads to an increased dermal bioavailability of poorly soluble actives. To avoid sedimentation of the porous particles (3–50 µm) in dermal formulations, viscoelastic gels were developed using ι–carrageenan, polyacrylate and the viscoelastic Kühne salad dressing as a reference from food industry. Silica particles (company Grace/US, 50 and 150 µm) were loaded into the gels and long-term stability was assessed by a VIS sedimentation test. Furthermore, the gels were characterized by analytical centrifugation (LUMiSizer®) to assess the critical rpm/g values, allowing to order them after their absolute viscoelastic stabilizing ability. Characterization was complemented by rotation rheology, amplitude sweep and a frequency sweep analysis for the determination of elastic and viscous moduli G′ and G′′ at varying conditions. Based on the throughout characterization, polymers can be selected to sufficiently stabilize dermal formulations even with large sized smartPearls® – the prerequisite for using this delivery system in dermal products.

Glabridin smartPearls – Silica selection, production, amorphous stability and enhanced solubility

Glabridin, a compound in the root extract of Glycyrrhiza glabra, has been identified as an effective tyrosinase inhibitor. Applied on skin, melanin synthesis is inhibited, making glabridin an interesting candidate for skin whitening or for the treatment of age spots. However, main obstaclefor its practical use is its low dermal bioavailability, caused by its poor water solubility. In this work smartPearls technology was used to increase the glabridins water solubility. smartPearls consist of silica particles with mesopores in which actives can be loaded. By this, actives are stabilized in amorphous state and simultaneously finely distributed in nm-range. Both amorphization and nanoization are well known approaches to increase saturation solubilities. In smartPearls these approaches are combined. In the first step, glabridin smartPearls formulation was developed, screening systematically the suitability of 4 different silicas varying in their pore sizes (3, 6, 10, 17 nm). Also, most suited filling level of glabridin was determined (25, 50, 80% referred to total pore volume of respective silica). Silica loading was performed by the immersion-evaporation method, resulting in pores filled with glabridin from bottom to top. By light microscopy, dynamic scanning calorimetry and X-ray diffraction the sample with 6 nm pore size and filling levels of 25% and 50% have been verified to be completely amorphous. Highest physical storage stability of 7 months up to now was obtained for the 25% filled sample. In the next step, concept of increased saturation solubility for smartPearls was proven. Dissolution profiles were recorded in situ for glabridin smartPearls and compared to glabridin raw drug powder. Both saturation solubility and dissolution velocity were remarkably improved. The water solubility for example increased by a factor of more than 4. This makes glabridin smartPearls promising for creating skin products with improved dermal bioavailability.

Novel skin penetrating berberine oleate complex capitalizing on hydrophobic ion pairing approach

Berberine hydrochloride (Brb) is a well-known herbal drug that holds a great promise in the recent years thanks to its various pharmacological actions. Currently, Brb is extensively researched as a natural surrogate with evidenced potentiality against numerous types of skin diseases including skin cancer. However, Brb’s high aqueous solubility and limited permeability hinder its clinical topical application. In the current work, to enhance Brb’s dermal availability, hydrophobic ion pairing approach was implemented combining the privileges of altering the solubility characteristics of Brb and the nanometric size that is usually gained during the ion pairing precipitation process. Sodium oleate (SO) was selected as the complexing agent due to its low toxicity and skin penetrating characteristics. Ion paired berberine oleate complex (Brb-OL) was prepared by simple precipitation technique. Brb-OL complex formation was confirmed by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffraction (XRD) and saturation solubility studies. It was found that Brb-OL complex formed at stoichiometric binding between oleate and Brb had an average particle size of 195.9 nm and zeta potential of −53.6 mV. The proposed Brb-OL showed 251-fold increase in saturation solubility in n-octanol which confirmed the augmented lipid solubility of the complex compared with free drug. Comparative in-vitro release study showed that Brb-OL complex had much slow and sustained release profile compared to that of free Brb. Furthermore, ex-vivo permeation study using rat skin revealed the enhanced skin permeation of ion-paired Brb-OL complex compared with free Brb. In-vivo study on healthy rats confirmed that topical application of hydrogels enriched with Brb-OL had superior skin penetration and deposition than free Brb as revealed by confocal microscope. Conclusively, ion pair formation between Brb and oleate lead to the formation of more lipophilic Brb-OL complex with nanometric particle size which is expected to be a major progressive step towards the development of a topical berberine formulation.

PREPARATION AND CHARACTERIZATION OF ORAL NANOSUSPENSION LOADED WITH CURCUMIN

Objective: The principle objective of the present research work was to improve the bioavailability of curcumin (CUR) by decreasing its particle size. Nanosuspension (NS) of CUR was prepared using poloxamer-188 (P188) as a surfactant. The prepared NSs were characterized for particle size, polydispersity index (PDI), zeta potential, drug loading, saturation solubility, and drug release kinetic studies.Methods: Components required for NS preparation, such as solvent, anti-solvent and surfactant were screened. Precipitation high-speed homogenization (HSH) method was used for the preparation of NS using selected components. Evaluation of NS for particle size, PDI, drug loading, saturation solubility and in vitro drug release was done. Pharmacokinetic studies of the NS in sprague dawley (SD) rats were performed.Results: The particle size, PDI and zeta potential of the optimized formulation was 596.5±5 nm, 0.233±0.010 and-23±2 mV respectively. The pH of all the formulations was in the range of 5-6 which is acceptable when related to drug stability. The optimized formulation showed an increase in saturation solubility in water and phosphate buffer pH 6.8 when compared to plain CUR suspension (S). Results of pharmacokinetic studies indicated that Cmax and AUC0-6 were increased 8 and 10 times respectively from plain CUR S to CUR NS.Conclusion: CUR NS was prepared using P188 as the stabilizer. Amongst various stabilizers screened P188 rendered a stable NS with the particle size in nano range. Pharmacokinetic studies revealed the better performance of CUR NS as compared to plain CUR S.

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. Milling of amorphous indomethacin with polyvinylpyrrolidone (PVP) as stabilizer resulted in an amorphous nanosuspension which could not be redispersed in the nanosize range after freeze-drying. The combination of PVP and poloxamer 407 resulted in crystalline nanoparticles: poloxamer 407, a polymer with high molecular weight, competed with PVP for surface coverage, and hindered the interaction between PVP and indomethacin. This indicated the importance of sufficient drug-PVP interactions on the drug particle surface for amorphous state stabilization. Redispersable amorphous indomethacin nanoparticles were obtained by combining the anti-recrystallization effect of PVP with the particle size stabilization provided by sodium dodecyl sulfate. Solubility studies were performed in situ. The solubility of crystalline micronized indomethacin of 6.7 ± 1.3 µg/mL was increased up to 17.3 ± 2.8 µg/mL by its amorphization, with a factor of increase of 2.6. Indomethacin amorphization increased its dissolution rate by a factor of 30. Indomethacin nanocrystals resulted in an increased solubility of 2.6 times, with a solubility of 17.2 ± 0.4 µg/mL. The highest increase was obtained with amorphous indomethacin nanoparticles with a solubility of 35 ± 1.6 µg/mL and 5.2 times higher than the solubility of the original indomethacin. Amorphous indomethacin nanoparticles resulted in the highest dissolution rate, which increased from 0.003 µg/(mL s) to 2.328 µg/(mL s). The synergistic effect obtained by the combination of nanosize and amorphous solid state was demonstrated.

Algal Nanosuspensions for Dermal and Oral Delivery

Background: Algae are widely used for their beneficial properties by food, cosmetic and nutraceutical industry. For nutraceutical and cosmetic (e.g. oral and dermal) application, solubility is a key parameter. Algal extracts are available in sticky and completely dried form and in both cases it is difficult to formulate them due to solubility challenges. Therefore, attempts were made to produce stable algal nanosuspensions. A nano algal suspension could increase the biological activity (due to increased saturation solubility and higher dissolution velocity) and lead to better penetration or absorption profile. Methods: Dried algae products (N. oculata and Chaetoceros) were obtained from biotechnological cultivation. The algae were dispersed in Tween 80 or in Poloxamer 188 solutions and passed through a piston-gap high pressure homogenizer to produce nano algal suspensions. Production parameters like, number of homogenisation cycles, pressure etc, were optimised. Nanosuspensions were evaluated for particle size, zeta potential and crystallinity. Furthermore, nanosuspensions were converted to solid product using lyophilisation and extrusion-spheronisation technique. Results: A minimum size of about 226 nm could be achieved after 10 cycles at 1,500 bar. The aqueous nanosuspensions showed highest, but still insufficient stability at refrigeration (4 months data), decreasing stability with increasing temperature, especially at 50°C in the stress storage test and during autoclaving at 121°C. Preservation with Euxyl PE 9010 further decreased the physical stability of the aqueous algae nanosuspensions. Algae as natural material undergoes chemical degradation when in contact with water. For long-term preservation of the size and for chemical stabilization, the algae nanosuspensions were lyophilized. The algae nanoparticles re-dispersed well in water when using trehalose as cryoprotectant. The lyophilizate can be filled in capsules. Pellets were produced using the nanosuspensions as granulation fluid, filled in gelatine capsules for nutraceutical delivery. Conclusion: Nano-algal suspensions open new perspective for algae products with enhanced bioavailability and penetration profile. The produced nanosuspensions can be used for dermal, nutraceutical or cosmetics purposes. Keywords: Algae, N. oculata, Chaetoceros, nanocrystals, dermal application, oral delivery, nutraceutical, nanonisation, nanosupensions.

Ziprasidone nanocrystals by wet media milling followed by spray drying and lyophilization: Formulation and process parameter optimization

The aim of work was to prepare and characterize Ziprasidone nanosuspension to achieve enhance solubility and in vitro dissolution. The media milling technique was utilized for production of nanosuspension and the effect of amount of milling agent, milling time, volume of water, stirring speed and type of stabilizers on particle size and size distribution was studied. The optimized nanosuspension was subjected to spray drying and lyophilization which than characterized for fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), in vitro dissolution study, X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). FTIR and DSC studies showed compatibility of Ziprasidone with selected excipients. DSC study also revealed that crystalline form of Ziprasidone in spray dried and lyophilized nanosuspension was remained same as to that of pure Ziprasidone. XRD of spray dried and lyophilized nanosuspension showed same diffraction pattern as that of the pure Ziprasidone only crystallinity was decreased. Around 8 fold increase in saturation solubility was observed. In vitro dissolution of spray dried and lyophilized nanosuspension was significantly higher. The rod like nanocrystals were observed in FE-SEM studies which were present on surface of sphere in spray dried nanosuspension and dispersed in matrix like structure in lyophilized nanosuspension.

A novel nanosuspension of andrographolide: Preparation, characterization and passive liver target evaluation in rats

Andrographolide (Andro) is an excellent anti-inflammatory bicyclic diterpene γ-lactone. However, the poor solubility limits its application as injection for the treatment of acute inflammation. To meet the clinical needs for emergency, the Andro nanosuspensions injection was first prepared by the wet milling technique. The Andro nanosuspensions were composed of 3% Andro, 5% poloxamer 188 as the non-ionic stabilizer, 0.05% sodium deoxycholate or 0.1% sodium tauroursodeoxy cholate as the ionic stabilizer, and prepared by 350rpm speed and 12cycles of grinding with 0.4mm zirconium oxide pearls. The nanosuspensions showed hexagonal morphology with particle size of 300nm, and no change in crystalline state of Andro after milling. The nanosuspensions had a significant increase in saturation solubility, and could completely release within 0.25h (bulk Andro within 24h). The lyophilized product of Andro nanosuspensions with mannitol (5%) as lyoprotectant had good physical and chemical stability during the 6-month storage period. The pharmacokinetic and tissue distribution results showed that it was rapidly eliminated from the blood and largely distributed in the liver. Overall, the Andro nanosuspensions may be used as a potential formulation for the treatment of liver infections owing to its passive liver targeting function.