Production, applications and in vivo fate of drug nanocrystals

Tuomela, Annika; Saarinen, Jukka; Strachan, Clare J.; Hirvonen, Jouni; Peltonen, Leena

doi:10.1016/j.jddst.2016.02.006

Cited by 34 publications

(17 citation statements)

References 75 publications

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“…Co‐crystalline drugs are often composed of multiple components, including a hydrophobic drug and a stabilizer. Stabilizers are supplementary molecules which when added during formulation, can control the nanocrystal size, agglomeration, and its overall biodistribution in vivo . Stabilizers are generally 50–500 fold more soluble in water than the drug in its free powder form.…”

Section: Preparation and Characterization Of Nanocrystalsmentioning

confidence: 99%

“…Stabilizers are supplementary molecules which when added during formulation, can control the nanocrystal size, agglomeration, and its overall biodistribution in vivo. 8,14 Stabilizers are generally 50-500 fold more soluble in water than the drug in its free powder form. When exposed to an aqueous environment, the stabilizer first begins to leach into solution and leaves behind the drug particles.…”

Section: Nanocrystal Drug Dissolution: Concept and Theorymentioning

confidence: 99%

“…Nanocrystalline drug technology improves the solubility of hydrophobic drugs due to an increased surface area to volume ratio and improved dissolution rates (i.e., dissolution velocity) associated with nanosizing. 8 The drug crystals are singularly well-suited for the rehabilitation of previously unsuccessful Biopharmaceutics Classification System (BCS) Class II and IV drugs (low solubility drugs). 9 The BCS classification system is an experimental model that measures permeability and solubility under prescribed conditions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nanocrystals: A perspective on translational research and clinical studies

Jarvis

Krishnan

Mitragotri

2018

Bioengineering & Transla Med

102

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Poorly soluble small molecules typically pose translational hurdles owing to their low solubility, low bioavailability, and formulation challenges. Nanocrystallization is a versatile method for salvaging poorly soluble drugs with the added benefit of a carrier‐free delivery system. In this review, we provide a comprehensive analysis of nanocrystals with emphasis on their clinical translation. Additionally, the review sheds light on clinically approved nanocrystal drug products as well as those in development.

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Section: Preparation and Characterization Of Nanocrystalsmentioning

confidence: 99%

Section: Nanocrystal Drug Dissolution: Concept and Theorymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nanocrystals: A perspective on translational research and clinical studies

Jarvis

Krishnan

Mitragotri

2018

Bioengineering & Transla Med

102

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“…The first technique developed and patented was Nanoedge ® , which couples a solvent/antisolvent precipitation step with an annealing step given by HPH [215]. Other combination processes are those included in the Smart Crystals ® technology, where the pre-treatment processes include all the A C C E P T E D M A N U S C R I P T 47 techniques mentioned above for the bottom-up production of nanocrystals, followed by HPH [216].…”

Section: Combination Of Bottom-up and Top-down Approachesmentioning

confidence: 99%

Production of pure drug nanocrystals and nano co-crystals by confinement methods

Fontana

Figueiredo

Zhang

et al. 2018

Advanced Drug Delivery Reviews

139

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The use of drug nanocrystals in the drug formulation is increasing due to the large number of poorly water-soluble drug compounds synthetized and due to the advantages brought by the nanonization process. The downsizing processes are done using a top-down approach (milling and homogenization currently employed at the industrial level), while the crystallization process is performed by bottom-up techniques (e.g., antisolvent precipitation, use of supercritical fluids or spray and freeze drying). In addition, the production of nanocrystals in confined environment can be achieved within microfluidics channels. This review analyzes the processes for the preparation of nanocrystals and co-crystals, divided by top-down and bottom-up approaches, together with their combinations. The combination of both strategies merges the favorable features of each process and avoids the disadvantages of single processes. Overall, the applicability of drug nanocrystals is highlighted by the widespread research on the production processes at the engineering, pharmaceutical, and nanotechnology level.

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“…The drug with functionally modified polymer of second generation nanocrystals enable the greater potential applications in delayed and drug delivery system of therapeutics. Novel possibilities for second generation nanocrystal applications are expedited by the polymeric nano crystal composite system as a modified delayed drug delivery carrier for oral drug delivery [5].…”

Section: Introductionmentioning

confidence: 99%

Influence of Poloxamer 188 on Design and Development of Second Generation PLGA Nanocrystals of Metformin Hydrochloride

Panda¹,

Krishnamoorthy²,

Shivashekaregowda³

et al. 2018

Nano BioMed ENG

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The poly(D,L-lactide-co-glycolide) (PLGA) based second-generation nanocrystals prepared by modified nanoprecipitation method, is the method of choice for encapsulation of both lipophilic and hydrophilic drugs. In this study, nanoprecipitation technique was adopted to develop second generation nanocrystals of PLGA loaded with metformin HCl (MHc). Poloxamer 188 with three different concentrations (0.5, 0.75, 1% w/v) in combination with PLGA at 1, 2, 3% concentrations (w/v) successfully produced MHc loaded PLGA second generation nanocrystals. The effects of poloxamer 188, amphiphilic triblock copolymer on carrier particle size, surface morphology, polydispersity index, zeta potential, drug entrapment efficiency and drug release of nanoformulation were investigated. The optimized formulation of second-generation nanocrystals with concentrations 0.75% w/v poloxamer 188 and 2% w/v PLGA, could produce particle size of 114.6 nm, entrapment efficiency of 63.48% and drug release 80.23% at 12 h. A blank formulation with the same composition as optimized formulation without addition of poloxamer188 compared with optimized formulation, exhibited nanoparticles of larger mean particle size of 212.9 nm with entrapment efficiency of 68.47% and 50.5% drug release at 12 h. Transmission electron microscopy (TEM) analysis of the nanoformulations revealed that poloxamer188 greatly contributed to smooth, spherical morphology of nanosize polymeric nanoparticles. Further Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on nanoformulation emphasized the significance of poloxamer188 in formulation and development of optimized MHc loaded PLGA nanosuspensions of second generation nanocrystals. In conclusion, the study emphasizes that poloxamer 188 was a versatile excipient, which played a pivotal role in producing nanosize carrier with high drug release profile of MHc loaded PLGA nanosuspensions of second generation nanocrystals.

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Production, applications and in vivo fate of drug nanocrystals

Cited by 34 publications

References 75 publications

Nanocrystals: A perspective on translational research and clinical studies

Nanocrystals: A perspective on translational research and clinical studies

Production of pure drug nanocrystals and nano co-crystals by confinement methods

Influence of Poloxamer 188 on Design and Development of Second Generation PLGA Nanocrystals of Metformin Hydrochloride

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