Pharmaceutical nanotechnology: from the bench to the market

Background Nanotechnology is considered a new and rapidly emerging area in the pharmaceutical and medicinal field. Nanoparticles, as drug delivery systems, impart several advantages concerning improved efficacy as well as reduced adverse drug reactions. Main body Different types of nanosystems have been fabricated including carbon nanotubes, paramagnetic nanoparticles, dendrimers, nanoemulsions, etc. Physicochemical properties of the starting materials and the selected method of preparation play a significant aspect in determining the shape and characteristics of the developed nanoparticles. Dispersion of preformed polymers, coacervation, polymerization, nano-spray drying and supercritical fluid technology are among the most extensively used techniques for the preparation of nanocarriers. Particle size, surface charge, surface hydrophobicity and drug release are the main factors affecting nanoparticles physical stability and biological performance of the incorporated drug. In clinical practice, many nanodrugs have been used for both diagnostic and therapeutic applications and are being investigated for various indications in clinical trials. Nanoparticles are used for the cure of kidney diseases, tuberculosis, skin conditions, Alzheimer’s disease, different types of cancer as well as preparation of COVID-19 vaccines. Conclusion In this review, we will confer the advantages, types, methods of preparation, characterization methods and some of the applications of nano-systems.

Development and characterization of ethanol-free spearmint essential oil nanoemulsion for food applications using the low energy technique

Different emulsifiable concentrates containing spearmint essential oil (SEO) were made and evaluated for their potential for giving ethanol-free nanoemulsion spontaneously upon dilution into water. Each one of these formulas had its specific composition regarding the type of excipients, surfactants, surfactant/SEO ratio and surfactant concentration. The results of this evaluation indicated that the chemical composition of SEO has a profound effect on the formation and physical stability of the nanoemulsion. The incorporation of excipients such as long chain triglyceride and propylene glycol into the emulsifiable concentrates at only 1.0% can lead to a stable nanoemulsion that resists Ostwald ripening. A particle size measurement showed that the diameter of SEO in the nanoemulsion was 28.2 nm and its nanostructure was maintained for 3 months. The application of a mixture of binary nonionic food-permitted surfactants enhanced the thermal stability of the nanoemulsion at up to 50 ᵒC. The developed ethanol-free SEO nanoemulsion has promising industrial applications in food and beverage flavoring.

Rheological Investigation of Lipid Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine (Conference Paper )#

The rheological behavior among factors that are present in Stokes law can be used to control the stability of the colloidal dispersion system. The felodipine lipid polymer hybrid nanocarriers (LPHNs) is an interesting colloidal dispersion system that is used for rheological characteristic analysis. The LPHNs compose of polymeric components and lipids. This research aims to prepare oral felodipine LPHNs to investigate the effect of independent variables on the rheological behavior of the nanosystem. The microwave-based technique was used to prepare felodipine LPHNs (H1-H9) successfully. All the formulations enter the characterization process for particle size and PDI to ascertain the colloidal properties of the prepared nanosystem then use coaxial rotational digital rheometer for rheological evaluation. The outcomes show that all felodipine LPHNs formulations (H1-H9) had a nanosize and homogenous structure that ascertain colloidal features of the nanodispersion system. The rheogram chart indicates that all of the felodipine LPHNs formulations (H1-H9) show pseudoplastic flow (non-Newtonian flow) that have shear-thinning property. The microwave-based method prepares felodipine LPHNs formulations (H1-H9) that show excellent physical texture that ascertains its ability as a technique for the preparation of nanoparticles. All of the felodipine LPHNs formulations (H1-H9) show pseudoplastic flow that supports the physical stability of the nanosystem.

Cyclodextrins-in-Liposomes: A Promising Delivery System for Lippia sidoides and Syzygium aromaticum Essential Oils

Biological activity of essential oils (EOs) has been extensively reported; however, their low aqueous solubility, high photosensitivity, and volatility compromise a broad industrial use of these compounds. To overcome these limitations, we proposed a nanoencapsulation approach to protect EOs, that aims to increase their stability and modulate their release profile. In this study, drug-in-cyclodextrin-in-liposomes encapsulating two essential oils (Lippia sidoides and Syzygium aromaticum) and their respective major compounds (thymol and eugenol) were produced by ethanol injection and freeze-dried to form proliposomes and further physicochemically characterized. Liposomes showed high physical stability over one month of storage at 4 °C, with slight changes in the mean size, polydispersity index (PDI), and zeta potential. Reconstituted proliposomes showed a mean size between 350 and 3300 nm, PDI from 0.29 to 0.41, and zeta potential between −22 and −26 mV. Differential scanning calorimetry and X-ray diffraction of proliposomes revealed a less-ordered crystalline structure, leading to high retention of the major bioactive compounds (between 73% and 93% for eugenol, and 74% and 84% for thymol). This work highlights the advantages of using drug-in-cyclodextrin-in-liposomes as delivery systems to retain volatile compounds, increasing their physicochemical stability and their promising potential to be utilized as carriers in products in the pharmaceutical, food, and cosmetic industries.

DIACEREIN-LOADED NIOSOMES (DC-NS): A NEW TECHNIQUE TO SUSTAIN THE RELEASE OF DRUG ACTION

Objective: The study's main goal is to develop a suitable niosomes (NS) encapsulated drug for anti-inflammatory effects such as diacerein (DC) and to evaluate the system's vesicle size (VS), entrapment efficiency (EE %), physical stability and in vitro release. Methods: Tween (40 and 60), cholesterol, and stearylamine were used in a 1:1:0.1 molar ratios as non-ionic surfactants. Thin film hydration was used to create the NS. Results: The higher EE% was observed with NS (F11) prepared from tween 60, cholesterol and 2.5 min sonication. These formulations' release patterns were Higuchi diffusion and first order. For the stability study, NS formulations were stored at temperature between 2-8 °C for 60 d retains the most drugs when compared to room and high temperature conditions. Conclusion: The findings of this study have conclusively shown that after NS encapsulation of DC, drug release is prolonged at a constant and controlled rate.

FORMULATION OF EFFERVESCENT GRANULES FROM RED GINGER (ZINGIBERIS OFFICINALE ROSCOE VAR. RUBRUM) EXTRACT AND ITS ANTIOXIDANT ACTIVITY

Objective: Ginger is one of the Indonesian plants that has been used as traditional medicine. The flavonoids and phenols compounds contained high antioxidant activity. This study aimed to formulate effervescent granules (EG) from red ginger (RG) extract and evaluate its antioxidant activity. Methods: The formulation of EG from RG extract was prepared by the wet granulation method using different concentrations of polyvinylpyrrolidone (PVP). Furthermore, the flowability of granules was evaluated, including flow rate, angle of repose, bulk density, tapped density, Carr's index, Hausner ratio, and effervescent time. The physical stability of granules such as organoleptic evaluation, effervescent time, and pH measurement was also evaluated after 28 d of storage, and the antioxidant activity of EG from RG extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Results: The result showed that the EG of RG extract was successfully prepared by wet granulation with a concentration of 15%. In addition, the flowability study showed that all formulas of EG from RG extract have good flow properties, and the granules showed excellent flow properties based on Carr′s index results. The effervescent time of granules remained within the acceptable range according to USP, and the physical stability did not change even after 28 d of storage. The IC50 of EG from RG extract was 283.28±3.6 ppm and has moderate in free radicals scavenging activity. Conclusion: EG from RG extract can be used as food supplements to protect the human body from free radicals and inhibit oxidases.

FORMULATION OF CINNAMON BARK ESSENTIAL OIL GEL AS MOSQUITO REPELLENT

Objective: The purpose of this research is to prepare a cinnamon bark essential oil gel preparation, determines the physical characteristic and physical stability during storage, and examines the activity of mosquito repellent from the best gel preparation. Methods: The formulations of gel were made with variations in the concentration of Carbopol 940 (0.5%, 1.5%, and 2%) contain 1% of cinnamon bark essential oil. The gel evaluated physical characteristics and physical stability. The parameters of organoleptic, homogeneity, and pH are analyzed descriptive, while the viscosity, the spreadability, and the gel adhesion were analyzed using one-way ANOVA at the level of confidence of 95%. The best gel tested its effectiveness as compared to the negative control and product innovator (which used DEET as an active compound) as a positive control. The activity of repellent was determined by an Aedes aegypti mosquito for 6 h with 2 hands respondents. The effectiveness of repellent protection is calculated by the percentage of protection power. Results: The studies showed that all the gel preparations qualified the organoleptic, homogeneity, and pH parameters. The viscosity, gel adhesion, and spreadability are also stable during storage. Conclusion: Based on the results, the best gel is the formula I which has mosquito repellent activity effective for 6 h like DEET.

Nanostructured-lipid carriers-Chitosan hydrogel beads carrier system for loading of resveratrol: A new method of topical application

The aim of this study was to develop nanostructured-lipid carriers (NLC) encapsulated by Chitosan hydrogel beads for the efficient topical carrier. Dynamic light scattering (DLS), X-ray diffraction (XRD), Differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were conducted to study the influence of the encapsulation on the characteristic of resveratrol-loaded NLC, and the results showed that there was no impact on resveratrol-loaded NLC. Chitosan hydrogel beads could significantly improve the physical stability of resveratrol-loaded NLC. In vitro release study revealed that resveratrol-loaded NLC-Chitosan hydrogel beads had a more significant sustained-release effect on resveratrol. In vitro transdermal studies suggested that the skin permeation of resveratrol was promoted by the effect of Chitosan hydrogel beads and increased resveratrol distribution in the skin. In vitro cytotoxicity showed that resveratrol-loaded NLC-Chitosan hydrogel beads did not exert a hazardous effect on L929 cells. Hence, NLC-Chitosan hydrogel beads might be a promising method for topical applications of resveratrol.

THE USE OF CARROT SEED OIL (DAUCUS CAROTA L.) TO FORMULATE NANOEMULGELS AS AN EFFECTIVE NATURAL SUNSCREEN AND SKIN ANTI-AGING

Objective: The purpose of this study was to develop a nanoemulgel containing vegetable oil of carrot seed oil as an effective natural sunscreen and skin anti-aging. Methods: Nanoemulgels containing 4% carrot seed oil were formulated in three formulas with different ratios of Tween 80 and Sorbitol and prepared by using the high-energy emulsification method. The nanoemulgels were determined for the organoleptic characteristic, globule size, pH, physical stability during storage for 12 w at three different temperatures (room, high and low temperature), centrifugation, and cycling test. The Sun Protection Factor (SPF) value was determined by UV spectrophotometric method and the effectiveness of anti-aging was evaluated by using a skin analyzer and the results were compared with sunscreen emulgel. Results: Nanoemulgel containing 4% carrot seed oil with a ratio of Tween 80 as surfactant and Sorbitol as co-surfactant 40 and 20 resulted in the smallest mean droplet size of 338.34 nm and the sizes were increased during 12 w of storage at room temperature but still in the nano size and this nanoemulgel did not show phase separation or still stable. These nanoemulgels were also stable after the centrifugation and cycling test. The emulgel preparation was not stable or showed phase separation after the centrifugation test. The SPF value obtained from the nanoemulgel was 20.28±0.22 and these values were higher than the sunscreen emulgel (13.94±0.27). The pore size, spot, and wrinkles of the volunteer skin were reduced after using the nanoemulgel containing 4% carrot seed. Conclusion: The sunscreen and skin anti-aging activity of nanoemulgel preparation containing 4% carrot seed oil with a ratio of surfactant Tween 80 and co-surfactant Sorbitol 40 and 20 were more effective compare with emulgel preparation.

Formulation of Cinchona Extract (Cinchona succirubra) Cream and The Safety as Hair Fertilizer

Background: cinchona extract contains quinoline alkaloids, has telangiectatic activity, is practically insoluble in water so penetration into hair follicles is low and requires a delivery system, namely cream. Objective: to determine the formula of cinchona extract cream with good activity, physical stability and safety. Methodology: cinchona bark extraction (soxhletation method), phytochemical screening, cinchona extract dosage determination, optimization of cream formula using Design Expert software version 11. Evaluation: pH, adhesion, spreadability, viscosity and cycling test stability. Activity test using guinea pigs (Cavia porcellus) for 14 days, parameters of hair length/2 days, hair mass (14th day). Acute dermal irritation test using rabbit (Orycogalus cuniculus) by erythema and edema index parameters. Results: cinchona extract (13.32% yield) contained quinoline alkaloids, cinchona extract dosage was 20% (p<0.05). The optimum formula is F2 with characteristics: pH 6.48±0.07, adhesion 1.16±0.07, spreadability 4.99±0.85 and viscosity 3067±416.45, has good physical stability. Activity test: test area hair length 13.54 – 62.14% longer than normal control and 10.10 – 49.17% than negative control. The hair mass of test area was 122.91% heavier than normal control and 104.48% of negative control (p<0.05). Cinchona extract and excipients were non-irritant. Conclusion: Cinchona extract cream (20%) has hair fertilizer activity, good physical stability and safety.