Dissolution rate limited bioavailability of flutamide, and in vitro – in vivo correlation

Posti, Juhani; Katila, Kirsi; Kostiainen, Timo

doi:10.1016/s0939-6411(99)00061-2

Cited by 14 publications

(3 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, many drugs in the pharmaceutical industry are of low aqueous solubility and thus dissolution rate becomes a limiting factor for bioavailability. It is well known that one approach to this problem is to perform particle size reduction, resulting in very fine particles and a larger surface area leading to an increase dissolution rate and consequently, bioavailability (1,2). In addition, a fine particle size is required for drugs administered via the pulmonary route (3,4).…”

Section: Introductionmentioning

confidence: 99%

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Saleem

Smyth

2010

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The air-jet and ball-mill are frequently used in fine micronization of active pharmaceutical ingredients to the order of 1-5 μm, which is important for increasing dissolution rates, and also for pulmonary delivery. In this study, we investigated the ability of air-jet and ball-mill to achieve adequate micronization on the lab scale using a model soft material, Pluronic® F-68. Material mechanical properties were characterized using the nanometer 600. Pluronic® F-68 was ball-milled in a micro-mill at different material weights and durations in liquid nitrogen vapor. In comparison, a lab scale air-jet mill was used at various milling parameters according to a full factorial design, where the response factors were particle yield and particle size distribution, which was analyzed using laser diffraction and scanning electron microscopy. The yield achieved with the micro-ball mill was 100% but was~80% for the air-jet mill, which reduced the size of Pluronic® F-68 from 70 μm to sizes ranging between 23-39 μm median diameters. Ball milling produced particles less than 10 μm after 15 min. Although air-jet milling proved capable of particle size reduction of the relatively soft material Pluronic® F-68, limitations to the lower size range achievable were observed. The feed rate of the material into the air jet mill was a significant factor and slower feed rates lead to smaller sizes by allowing more time for particle collisions and subsequent particle breakage to occur. Micro-ball milling under cold condition was more successful at achieving a lower range particle size reduction of soft materials.

show abstract

Section: Introductionmentioning

confidence: 99%

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Saleem

Smyth

2010

AAPS PharmSciTech

View full text Add to dashboard Cite

show abstract

“…Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor and is used to treat androgen-sensitive prostate carcinoma. It has low oral BA due to its low aqueous solubility and extensive first-pass metabolism [94]. Youssef et al formulated flutamide-containing polymerosomes using amphiphilic copolymer polyethylneglycol-polycaprolactone (PEG-PCL) as stable and sustained release formulation [22].…”

Section: Flutamidementioning

confidence: 99%

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

Lee

2020

Pharmaceutics

188

View full text Add to dashboard Cite

It has been known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability (BA). The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase dissolution and subsequently absorption in the gastrointestinal (GI) tract because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, there have been several drawbacks, such as structural instability in the GI tract and poor permeability across intestinal epithelia because of its relatively large size. In addition, there have been no liposomal formulations approved for oral use to date, despite the success of parenteral liposomes. Nevertheless, liposomal oral delivery has resurged with the rapid increase of published studies in the last decade. However, it is discouraging that most of this research has been in vitro studies only and there have not been many water-insoluble drugs with in vivo data. The present review focused on the in vivo evidence for the improved BA of water-insoluble drugs using liposomes to resolve doubts raised concerning liposomal oral delivery and attempted to provide insight by highlighting the approaches used for in vivo achievements.Pharmaceutics 2020, 12, 264 2 of 30 However, there have been several drawbacks to be overcome, such as instability in the GI tract and poor permeability across the intestinal epithelia because of liposomes' relatively large size [8]. Moreover, it seemed that liposomal oral delivery was faltering during 1980s due to some disappointing results for insulin [9]. However, liposomal oral delivery resurged with a rapid increase in the number of papers published, as shown in Pubmed search results, mainly due to various advanced modification technologies, even though liposomal oral delivery-related papers account for only 5-6% of the total number of liposomes-related studies (Figure 1). In addition, there was an encouraging meta-analysis report in which phospholipid-based solid formulations were analyzed as being effective for BA enhancement [10]. Although liposomal delivery does not seem to achieve satisfactory improvement of oral BA for peptides and protein drugs yet, it looks more promising for oral delivery of hydrophobic drugs because liposomes can solubilize poorly water-soluble drugs, protect the drug from degradation in the GI tract and enhance permeability through the epithelial cell membrane, consequently increasing oral BA. However, most published papers performed in vitro studies only, thus lacking in vivo pharmacokinetic results. The present review focuses on the in vivo evidence for the improved BA of water-insoluble drugs and highlights the approaches used for in vivo achievements.

show abstract

“…The common side effects of flutamide include hepatotoxicity, nausea, and diarrhea. Flutamide gets metabolized into 2-hydroxyflutamide, which also possesses anti-androgenic properties [13,14]. Table 1 represents flutamide loaded nanoformulations and its biological applications [15][16][17][18][19][20].…”

Section: Flutamidementioning

confidence: 99%

Nanoemulsions for Prostrate Cancer Therapy: An Overview

Manikandan

2017

Asian J Pharm Clin Res

View full text Add to dashboard Cite

The objective of this review is to focus the inferences of low/poor bioavailability and lack of dose proportionality for the oral delivery of drugs in prostatecancer therapy. To overcome such problems, various formulation strategies has been reported including various methods for the use of surfactants,cyclodextrins, solid dispersions, micronization, permeation enhancers, and lipids. Flutamide is an antiandrogen drug and used for the therapy of prostate cancer. The flutamide drug is having limited clinical application due to its poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. The lipid-based formulations such as nanoemulsion have been shown to improve the solubility and oral absorption of lipophilic drugs. To conclude, this article emphasizes the various approaches of nanoemulsion based formulation for prostate cancer therapy.Keywords: Nanoemulsion, Prostate cancer, Flutamide, Antiandrogen drug, Lipophilic drugs.

show abstract

Dissolution rate limited bioavailability of flutamide, and in vitro – in vivo correlation

Cited by 14 publications

References 1 publication

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

Nanoemulsions for Prostrate Cancer Therapy: An Overview

Contact Info

Product

Resources

About