A Novel Technique of Solubility Enhancement: Nanocrystals
A Novel Technique of Solubility Enhancement: Nanocrystals
A Novel Technique of Solubility Enhancement: Nanocrystals
ISSN No:-2456-2165
1 2
Jyoti Malik Anurag Khatkar
Affiliation: Research Scholar, Affiliation: Associate Professor,
Department of Pharmaceutical Sciences Department of Pharmaceutical Sciences
Field of expertise: Pharmaceutical Sciences Field of expertise: Pharmaceutical Research
Full Postal Address: Department of Pharmaceutical Full Postal Address: Department of Pharmaceutical
Sciences, MDU, Rohtak (Haryana), India Sciences, MDU, Rohtak (Haryana), India
3*
Arun Nanda
Affiliation: Professor,
Department of Pharmaceutical Sciences
Field of expertise: Pharmaceutical Research
Full Postal Address: Department of Pharmaceutical Sciences, MDU, Rohtak (Haryana), India
Abstract:- In the modern era, poor solubility is one of research, the solubility of medicinal molecules made from
the major problems preventing drugs to reach to co-crystals has increased by 4–20 times. Due to the
market. There are several methods for improving the extremely low oral absorption, it is still a significant
solubility of medications that are poorly soluble. difficulty for the pharmaceutical industry to generate
Nanocrystals have been identified as a helpful and suitable co-crystals for medicinal medicines. Compared to
effective method of drug delivery. Nanocrystals are a co-crystals, nano-cocrystals (NCs) can further increase a
family of solid medications that combine the principle of drug's solubility by having crystals in the nanometer size
nanoscience with the crystal structure to produce range. Furthermore, several scientists claimed that nano
benefits in the area of dissolution rate and formulations are frequently dispersed to increase their
physicochemical properties. Various techniques are now stability. Co-crystals structure contributes to sufficiently
available to prepare nanocrystals. In this review, a enhance the bioavailability and dissolving rate of less
detailed insight on conventional and recent techniques of soluble natural compounds, and nano-scale particles with
nanocrystals preparation along with route of larger surface areas also have an impact on these properties
administration, merits, and demerits of nanocrystals, has [2]. Another noteworthy benefit of nano-crystals is their
been provided. In addition, various nanocrystals nearly complete drug content, which increases the likelihood
formulations prepared by various researchers, of achieving high therapeutic levels and the desired
characterization and marketed formulation with pharmacological effects, and sets them apart from
formulations available in clinical phase are summarized conventional colloidal drug delivery technologies. Because
in this review. Quantum dots also termed semiconductor they may be administered in several ways, such as
nanocrystals and Wulff construction are also discussed. injectable, ocular, oral, and pulmonary, they are incredibly
versatile [3]. Co-solvents or solubilizing molecules are
Keywords:- Nanocrystals, Solubility, Quantum Dots, another approach that has been employed to improve the
Cocrystals, Nanotechnology. solubility of drugs that have low water solubility. Because of
the solubilizing molecules or residues of organic solvents,
I. INTRODUCTION this raises the risk of adverse effects or toxic reactions in the
body. Thus, it is imperative to find safe and effective ways
According to reports, up to 70% of drugs currently to increase methods to improve the solubility and
being developed by the pharmaceutical industry have bioavailability of medications that are poorly have low water
low aqueous solubility, which can impair drug development solubility [4].
due to the dangers of poor oral bioavailability and viability
problems in pharmacologic and toxicological studies. Nearly Nanocrystals
40% of currently marketed drugs also have this problem [1]. It is thought that nanocrystals were the catalyst for the
This challenge serves as a major impetus for scientists to development of modern nanoscience, which started in the
explore methods for enhancing the biopharmaceutical early 1980s and is still going strong today [5]. Nanocrystals
properties of pharmaceutical products. Co-crystals have a lot are solid, pure medicine particles have a size within
of potential uses for improving solubility. According to nanometer range. These compounds are 100% medicines,
Combination Techniques
Nanoedge Process:
It was the first integrated process for lowering the
particle size designed for the manufacturing of nanodrugs.
The precipitation method is used in conjunction with the
high pressure homogenization (HPH) technique.
Precipitation is employed to create the initial crystal
particles, which decreases HPH slit obstruction and
increases the effectiveness of particle size reduction during
the homogenization technique [27]. In order to better grind
the particles and avoid secondary growth as well as the
issues with unequal particle size distribution and ostwald
ripening in the precipitation approach, the homogenization
Fig 2 Recent Techniques of Nanocrystals Preparation procedure from the HPH method is utilised. As a result, the
nanocrytal particles are more physically stable [28].
Top-Down Techniques
Smart Crystal Process:
Laser Ablation: The basic components of smartcrystal technology are a
The solid target is exposed to laser light during laser pre-treatment stage and a HPH phase. Precipitation, spray
ablation, and the material that is expelled condenses into drying, freeze drying, or wet bead milling are a few
nanoparticles in the liquid around it. After that, the laser examples of pre-treatment steps that HPH can accompany
light converted stirred suspensions of microparticles into [29]. Smartcrystal process is acknowledged as a 2nd
nanoparticles [23]. The intensity of laser, the speed of generation technique for producing nanocrystals [30]. It uses
scanning, the characteristics of the suspension and other combination technology (CT), H69, H42 and H69
factors all have an impact on particle size. Although there approaches.
are no organic solvents used in this procedure, a tiny amount
of the medicine might experience oxidative degradation and H69:
crystal state alterations as a result of using too much power. H69, which combines nanoprecipitation and HPH
The production of nanosuspensions containing paclitaxel, techniques, is related to nanoedge technology. The high
megestrol acetate, and curcumin has been accomplished pressure homogeneous cavitation zone is where nanocrystals
using this technique [24]. are formed, which results in extremely tiny and
homogeneous particle sizes [31]
Ultrasound:
Through acoustic wave vibration, ultrasound is an H42 and H96:
effective way to fragment medication particles into smaller This approach is paired with a different technique, such
ones. The fast dispersion of drug solution and the creation of as freeze drying, spray drying, or HPH. To create drug
acoustic cavitation in solution caused by ultrasound have nanocrystals, the mixture of an insoluble drug and a
been proven to promote nucleation. It is frequently used in stabiliser is first spray/freeze dried, evenly scattered
combination with other methods due to its simplicity of use throughout the stabiliser skeleton, and then redispersed in
and good reproducibility in the laboratory. The length of the the water using HPH. Combining the two techniques
horn, the immersion depth of the horn, the cavitation depth, decreases particle agglomeration and boots processing
and the strength of the ultrasonic treatment all affect the effectiveness. It is appropriate for industrial-scale
nanocrystal’s size [25]. manufacturing [32].
Characterization Techniques of Nanocrystals height, are assessed using atomic force microscopy [90]. A
highly developed label-free technique called surface
X – Ray Diffraction (XRD): plasmon resonance (SPR) is used to look at how nanocrystal
To determine the crystallinity of a medication, the surfaces change, how well films disperse, and how well
XRD method is commonly utilised. The modification of the particles stick to one another [91].
polymorphic form served as evidence that the nanocrystals
had really been formed. The crystalline compounds’ XRD Thermal Analysis:
patterns are correlated with those of the pure substance. One of key techniques for examining the
Every crystalline compound creates a distinct pattern, and thermodynamic properties of drug nanocrystals is DSC. To
the combination of the each compound reveals its pattern. A assess the thermal behaviour, the drug’s crystallinity and the
particle’s unique fingerprint is shown by its XRD pattern production of nanocrystals using different polymers are
[87]. examined. For those medications that come in a variety of
polymorphic forms, this study is essential [92].
Morphological Analysis: Thermogravimetric analysis (TGA) helps to assess the
The size, structure and appearance of the NCs are sample’s quality while it is being heated and identify a
evaluated utilizing the scanning electron microscopy (SEM) solvent or hydrate’s structure [93].
and transmission electron microscopy (TEM). For TEM
examination, a wet sample with the right concentration is Raman Spectroscopy:
needed, but for SEM analysis, the generated nanosuspension This method relies on the inelastic scattering of laser-
must be transformed into a dried via lyophilisation / spray generated monochromatic light. The inelastic scattering is
drying, which causes aggregation [88]. Certain ingredients defined as the modification of the frequency of photon in
are introduced as protectants when the particle size increases monochromatic light due to contact with the material. The
significantly. Mannitol is frequently used as a cryo- sample absorbs the laser photon light, which is subsequently
protectant during the lyophilisation process to eliminate reemitted. In compared to the frequency of the initial
water. It also reduces particle agglomeration and monochromatic light, the photons’ remission frequency is
association. The final particle may aggregate up to certain moved down or up. This process is termed as Raman Effect.
extent within the acceptable range [89]. Additionally, the This shifting gives details about the compounds’ low-
surface characteristics like as friction, magnetism and frequency rotational, vibrational, and other transitions. It is
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