Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

Malamatari, Maria; Somavarapu, Satyanarayana; Taylor, Kevin; Buckton, Graham

doi:10.1517/17425247.2016.1142524

Cited by 70 publications

(35 citation statements)

References 91 publications

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“…Mannitol is a commonly used matrix former during the solidification of aqueous nanosuspensions, for both oral and pulmonary drug delivery (Malamatari et al, 2016). It is usually incorporated prior to spray drying due to its high aqueous solubility, and forms a continuous matrix around the drug nanocrystals enhancing their redispresibility on rehydration (Chaubal and Popescu, 2008;Yue et al, 2013).…”

Section: Preparation Of Microcomposite Particlesmentioning

confidence: 99%

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

Malamatari¹,

Somavarapu²,

Kachrimanis

et al. 2016

International Journal of Pharmaceutics

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Inhalable theophylline particles with various amounts of mannitol were prepared by combining wet milling in isopropanol followed by spray drying. The effect of mannitol as a co-milling agent on the micromeritic properties, solid state and aerosol performance of the engineered particles was investigated. Crystal morphology modelling and geometric lattice matching calculations were employed to gain insight into the intermolecular interactions that may influence the mechanical properties of theophylline and mannitol. The addition of mannitol facilitated the size reduction of the needle-like crystals of theophylline and also their assembly in microcomposites by forming a porous structure of mannitol nanocrystals wherein theophylline particles are embedded. The microcomposites were found to be in the same crystalline state as the starting material(s) ensuring their long-term physical stability upon storage. Incorporation of mannitol resulted in microcomposite particles with smaller size, more spherical shape and increased porosity. The aerosol performance of the microcomposites was markedly enhanced compared to the spray-dried suspension of theophylline wet milled without mannitol. Overall, wet co-milling with mannitol in an organic solvent followed by spray drying may be used as a formulation approach for producing respirable particles of water-soluble drugs or drugs that are prone to crystal transformation in an aqueous environment (i.e. formation of hydrates).

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Section: Preparation Of Microcomposite Particlesmentioning

confidence: 99%

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

Malamatari¹,

Somavarapu²,

Kachrimanis

et al. 2016

International Journal of Pharmaceutics

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“…Most frequently used solidification methods include spray and freeze-drying techniques. Redispersibility of solid nanocrystalline formulations is essential for potential oral and pulmonary clinical application [52].…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Emerging role of nanosuspensions in drug delivery systems

2020

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Rapid advancement in drug discovery process is leading to a number of potential new drug candidates having excellent drug efficacy but limited aqueous solubility. By virtue of the submicron particle size and distinct physicochemical properties, nanosuspension has the potential ability to tackle many formulation and drug delivery issues typically associated with poorly water and lipid soluble drugs. Conventional size reduction equipment such as media mill and high-pressure homogenizers and formulation approaches such as precipitation, emulsion-solvent evaporation, solvent diffusion and microemulsion techniques can be successfully implemented to prepare and scale-up nanosuspensions. Maintaining the stability in solution as well as in solid state, resuspendability without aggregation are the key factors to be considered for the successful production and scale-up of nanosuspensions. Due to the considerable enhancement of bioavailability, adaptability for surface modification and mucoadhesion for drug targeting have significantly expanded the scope of this novel formulation strategy. The application of nanosuspensions in different drug delivery systems such as oral, ocular, brain, topical, buccal, nasal and transdermal routes are currently undergoing extensive research. Oral drug delivery of nanosuspension with receptor mediated endocytosis has the promising ability to resolve most permeability limited absorption and hepatic first-pass metabolism related issues adversely affecting bioavailability. Advancement of enabling technologies such as nanosuspension can solve many formulation challenges currently faced among protein and peptide-based pharmaceuticals.

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“…The solubility of nanocrystals are appropriate due to their very high surface area and they can be incorporated into oral products by numerous methods of solidification such as spray drying (65), lyophilization (66), and electro-spraying (67). Physical and chemical stability of liquid nanosuspensions were improved by solidification methods.…”

Section: Nanocrystal Formationmentioning

confidence: 99%

Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

Moradpour

Barghi

2019

J Pharm Pharm Sci

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Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.

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Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

Cited by 70 publications

References 91 publications

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

Emerging role of nanosuspensions in drug delivery systems

Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

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