Investigation of Solubility Enhancement of Prasugrel Hydrochloride: Nanosuspensions and Cyclodextrin Inclusion Complexes (original) (raw)
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Design and characterisation of lopinavir nanocrystals for solubility and dissolution enhancement
Pharmaceutical Sciences Asia, 2019
The objective of present work was to prepare nanocrystals of Lopinavir (LPN) to enhance its solubility and dissolution rate with aim of dose reduction and minimising the side effects associated with it's oral administration. Nanocrystals of LPN were prepared by anti-solvent precipitation method using a 3 2 full factorial design, employing stirring speed (X1) and concentration of surfactant (X2) as independent variables. The nanocrystals obtained were characterised mainly for particle size (PS), zeta potential (ZP), crystallinity, saturation solubility, in vitro dissolution and permeability. Results demonstrated profound effect of concentration of surfactant (pluronic F-68) on both the PS and polydispersity index (PDI) values. The optimised nanocrystals formulation had particle size 265nm, PDI 0.260 and ZP in the range of-18.0 to-22.5mv. X-Ray diffraction studies (XRPD) and Differential scanning calorimetry (DSC) studies suggested nanocrystal formation and absence of crystalline peaks, indicating loss of crystallinity, additionally confirmed by scanning electron microscopy (SEM). Nanocrystals showed 30.45 fold enhancements in aqueous solubility, and 38.5 fold in phosphate buffer pH 6.8, as compared to pure LPN. In vitro release studies have demonstrated 92.20% cumulative drug release within 3 hrs from nanocrystals compared to 42.65% from pure LPN. Even, increase in permeation flux from 423.1 μg/cm 2 /hr to 632.93 μg/cm 2 /hr in case of nanocrystals was also indication of enhanced dissolution. Stable LPN nanocrystals formulated by anti-solvent precipitation method shows improved solubility and dissolution. It has been concluded that LPN nanocrystals were obtained with significant improvement in saturation solubility and drug losing it's crystalline nature when compared with plain drug.
Der Pharmacia Lettre, 2015
Nebivolol hydrochloride is a poorly water soluble drug falls under class II biopharmaceutical classification system, which is β 1 receptor antagonist that leads to vasodilatation, decreased peripheral vascular resistance, lowers blood pressure and heart rate. The rate of its oral absorption is often controlled by dissolution rate in the gastro intestinal tract. The aim of the present investigation was to improve the solubility and dissolution rate of poorly soluble drug, nebivolol hydrochloride by nanosuspension tablet prepared using microcrystalline cellulose PH101 (MCC) as diluent, povidone k 30 as binder and croscarmellose sodium as disintegrating agent. The formulation development work was performed by wet granulation method. The prepared granules and tablets were evaluated for various pre and post compression parameters as per IP and all the formulations are as per standards. Nebivolol nanosuspensions were prepared using solvent displacement/nanoprecipitation method. Among all the formulations F6 formulation has given the best dissolution studies (98.93%) and disintegration time (12.80 sec). In-vitro dissolution studies showed maximum (98.93%) release of drug within 15 minutes (F6) and mechanism of drug release from the tablets was followed first order kinetics. The optimized formulation (F6) is further selected and compared with the in-vitro drug release of innovator product (Nebilet) it showed 98.37% release of drug within 60 minutes and pure drug 27.34% within 60 minutes. Enhanced drug release rates were observed by nanosuspension tablets when compared to pure drug and innovator product (Nebilet). The physicochemical compatibility of the drug and excipients were studied by infrared spectroscopy and differential scanning calorimetry. The crystalline state of nebivolol hydrochloride drug state was changed to amorphous state due to nanosuspension formation and was confirmed by powderd X-ray diffraction study. Fourier transform infrared spectroscopy results revealed that there was no interaction between drug and excipients and results showed that there were no known chemical interactions of drug with excipient in formulation. It is concluded nanosuspension tablets were successfully prepared and they have demonstrated dramatic improvement in dissolution rate of the active drug.
Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs
International Journal of Pharmaceutics, 2006
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.
Advances in Pharmacology and Pharmacy, 2023
The formulation development of a drug is majorly based on the solubility of drugs. Nearly 40% of newly developed drugs show poor water solubility. Several approaches are used for the increasing solubility of such drugs for formulation development. Nanosuspension is one such attractive tactic which can be used for the enhancement of solubility, stability as well as bioavailability of such drugs. Nanosuspension can be defined as a two-phasic dosage form where solid drug particles of size less than 1 μm are dispersed in an aqueous phase with the help of a stabilizer. Particle size reduction in the nanoscale causes an increase in the surface area leading to an increase in dissolution rate and ultimately bioavailability is increased. A variety of excipients are used for the formulation of nanosuspension. Stabilizers, surfactants, co-surfactants, natural as well as organic solvents, buffers, salts, polyols, osmogents, and cryoprotectants are used in the formulation of nanosuspension. Various methods used in the formulation of nanosuspension can be classified into top-down and bottom-up approaches. Wet milling, high-pressure homogenization, anti-solvent techniques, melt emulsification, supercritical fluid extraction and ultrasonic homogenization are some of the methods for the preparation of nanosuspension. These methods are easy and appropriate for all poor water-soluble drugs. Nanosuspensions technology can be applied for the preparation of oral, pulmonary, injectable, ocular as well as targeted drug delivery. This review emphasizes various advantages and disadvantages of nanosuspension, its methods of preparation, formulation approaches, evaluation parameters, pharmaceutical applications, marketed products and patents of nanosuspension.
Nanosuspension: a novel approach to enhance solubility of poorly water soluble drugs- A review
2016
Solubility is the crucial factor for drug effectiveness, independence of the route of administration. Large proportion of newly discovered drugs are water insoluble & therefore poorly bioavailable contributing to desert development effort. Nanosuspensions have emerged as a promising strategy for the efficicent delivery of hydrophilic drugs because of their versatile features &unique advantages. The reduction of drug particles into submicron range leads to a significant increase in dissolution rate & therefore enhances bioavailability. Nanosuspension contain submicron colloidal dispersion of the pharmaceutical active ingredient particles in a liquid phase stabilised by surfactant. Nanosuspensions can be delivered by oral & non-oral route of administration. Study is focused on various methods of preparation with advantages & disadvantages, characterization properties, applications.
Nanosuspensions: A Strategy for Improved Bioavailability
2013
Poor aqueous solubility of lead drug candidates remains an obstacle for drug development in pharmaceutical industries. Drugs with dissolution rate limited drug absorption show low bioavailability due to poor aqueous solubility of the drug. To overcome these problems different formulations of nanosized drugs were developed recently. Pharmaceutical nanosuspensions consist of dispersed solid drug particles in an aqueous vehicle with average particle sizes below 1μm. The present paper is a review of current development in nanosuspension formulation strategies for possible improvement in oral bioavailability.
Nanosuspensions in Pharmaceutical Sciences: A Comprehensive Review
International Journal of Health Sciences and Research, 2023
Regardless of the method of administration, the solubility of drugs is essential to their efficiency. However, many newly discovered drugs suffer from poor water solubility and low bioavailability, leading to limited development efforts. Nanosuspension technology offers a solution for these "Brickellia" candidates by enhancing their solubility and bioavailability. Nanosuspensions improve medication stability and can be easily prepared for water-insoluble drugs using techniques such as highpressure homogenizers, wet mills and emulsion solvent evaporation. Additives like stabilizers, solvents, buffers, salts, and cryoprotectants can be used. Nanosuspensions can be administered orally, parenterally, intravenously, and can be combined with ocular inserts and mucoadhesive hydrogels for targeted drug delivery.
International Journal of Pharmaceutical Sciences and Drug Research, 2016
In this research work, the effects of nonionic stabilizers on the physical stability of drug nanosuspensions were investigated. For this purpose five nonionic polymers (hydroxypropylmethyl cellulose (HPMC), Hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and pluronic F68) and esomeprazole were selected as stabilizers and drug candidate, respectively. All the nanosuspensions were prepared using bottom up approach. The potential of Ostwald ripening for the nanosuspensions was investigated by subjecting them to various stress conditions such as storage at various temperature conditions (15°C, 25°C, 35°C, 45°C), mechanically shaking for 72 hours and fluctuation in storage temperature. All the polyvinylpyrrolidone and hydroxypropyl cellulose based formulations that were stored under different stress conditions exhibited the increase in particle size. In other cases the highest increase in mean particle size was observed at 45oC, followed by 35°C. Sample...
Nanosizing techniques are important tools for improving the bioavailability of water insoluble drugs. Here, a rapid wet milling method was employed to prepare nanosuspensions: 4 types of stabilizers at 4 different concentrations were tested on 2 structurally different drug compounds: indomethacin and itraconazole. Photon correlation spectroscopy (PCS) results showed that the finest nanosuspensions were obtained when 80 wt% (to drug amount) pluronic F68 was the stabilizer for indomethacin and 60 wt% pluronic F127 for itraconazole. Compared to physical mixtures, dissolution rates of the nanosuspensions showed significant increases. The morphology of nanoparticles was observed by transmission electron microscopy (TEM). Crystalline state of the drugs before and after milling was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The physical and chemical stabilities of the nanosuspensions after storage for 2 months at room temperature and at 4 • C were investigated using PCS, TEM and HPLC. No obvious changes in particle size and morphology and no chemical degradation of the drug ingredients were seen.
European Journal of Molecular & Clinical Medicine, 2021
Gemfibrozil is a lipid regulating agent that decreases serum triglycerides and very low density lipoprotein cholesterol and increases high-density lipoprotein (HDL) cholesterol. According to the Biopharmaceutical Classification System, GEM is classified under class-II drugs.Class-II drugs are the drugs with poor solubility and high permeation in the human body and pose problems in their pharmaceutical product development process. The aim of this work is to prepare GEM nanosuspensions using a precipitation ultrasonication method to increase its water solubility. The prepared nanosuspension was evaluated for Percent transmitance and in vitro dissolution. A Box behnken design was employed to study the effect of the independent variables i.e drug concentration in organic phase (mg/ml) at levels 20, 50 and 80 mg/ml (X1), Polyvinyl alcohol concentration at 0.1, 0.3 and 0.5 % (X2) and Sonication time at levels 10, 20 and 30 minutes (X3) on the dependent variables (i.e., percentage of drug released after 90min).The resulting data were fitted into Design Expert software and analysed statistically using analysis of variance (ANOVA). The data were also subjected to 3-D response surface methodology to determine the influence of concentration of Drug , PVA concentration and sonication time on dependent variable.The results show that nanosuspensions prepared with the higher concentrations of drug , the higher quantities of PVA and higher sonication time reduced the particle size and enhanced the dissolution rate of the formulation. The dissolution rate of the optimized nanosuspension Formulation was enhanced (96.2% in 90 min) mainly because of the formation of nanosized particles. The particle size of optimized nanosuspension was 191.0 nm and zeta potential was-12mV which is enough for sufficient electrostatic stabilization of Gemfibrozil nanosuspension. The X-ray powder diffraction and differential scanning calorimetry results indicated that the amorphization of gemfibrozil ra crystal and convert into nanocrystalline form and presence of drug. Conclusively, nanosuspension of gemfibrozil prepared using precipitation ultrasonication method showed improved solubility as compare with pure gemfibrozil.