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Fulltext Economic evaluation of combination therapy versus monotherapy for treatment of benign prostatic hyperplasia in Hong Kong

Wu DB, Yee CH, Ng CF, Lee SWH, Chaiyakunapruk N, Chang YS, et al.

Front Pharmacol, 2018;9:1078.
PMID: 30386234 DOI: 10.3389/fphar.2018.01078

Background: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a common condition affecting men. Studies have shown that the prevalence of LUTS/BPH increases with age, which will cause considerable economic burden to the healthcare system and society. The aim of the present study was to evaluate the long term cost effectiveness of dutasteride and tamsulosin therapy compared to tamsulosin alone in men with BPH in Hong Kong. Methods: A Markov decision model was constructed to estimate the economic impact from a healthcare payers' perspective, which only included direct costs. Analyses were conducted for a 4-year time frame. Results: When compared to tamsulosin alone, combination therapy was more expensive but also more effective in preventing complications and reduced the need for surgery. Over life-time projection suggest that combination therapy will be cost-effective if the willingness-to pay threshold of USD 20,000. Conclusion: Findings of this study found that combination therapy of tamsulosin and dutasteride was more cost-effective compared to tamsulosin alone across a wide range of scenario.

Matched MeSH terms: Dutasteride
Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery

Noor NM, Sheikh K, Somavarapu S, Taylor KMG

Eur J Pharm Biopharm, 2017 Aug;117:372-384.
PMID: 28412472 DOI: 10.1016/j.ejpb.2017.04.012

Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using1H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 23full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09μg/cm2) without coating and those coated with 5% CSO-SA (2.82±0.40μg/cm2), 10% CSO-SA (2.70±0.35μg/cm2) and CSO (2.11±0.64μg/cm2). There was a significant difference (p<0.05) in the cytotoxicity (IC50) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth.

Matched MeSH terms: Dutasteride/administration & dosage; Dutasteride/chemistry*
Fulltext In Vitro Performance of Dutasteride-Nanostructured Lipid Carriers Coated with Lauric Acid-Chitosan Oligomer for Dermal Delivery

Noor NM, Abdul-Aziz A, Sheikh K, Somavarapu S, Taylor KMG

Pharmaceutics, 2020 Oct 20;12(10).
PMID: 33092119 DOI: 10.3390/pharmaceutics12100994

Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (-18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4-8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride.

Matched MeSH terms: Dutasteride
In-Vitro and In-Vivo Evaluation of Supersaturable Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Dutasteride

Subramanian P, Rajnikanth PS, Kumar M, Chidambram K

Curr Drug Deliv, 2020;17(1):74-86.
PMID: 31721703 DOI: 10.2174/1567201816666191112111610

OBJECTIVE: A novel, Supersaturable Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) has been prepared to improve the Dutasteride's poor aqueous solubility.
METHODS: By adding Hydroxy Propyl Methyl Cellulose (HPMC) as a precipitation inhibitor to conventional SNEDDS, a supersaturable system was prepared. Firstly, the prepared SNEDDS played an important role in increasing the aqueous solubility and hence oral absorption due to nano-range size. Secondly, the S-SNEDDS found to be advantageous over SNEDDS for having a higher drug load and inhibition of dilution precipitation of Dutasteride. Formulated S-SNEDDS (F1-F9) ranged from 37.42 ± 1.02 to 68.92 ± 0.09 nm with PDI 0.219-0.34 and drug loading of over 95 percent.
RESULTS: The study of in-vitro dissolution revealed higher dissolution for S-SNEDDS compared to SNEDDS and Avodart soft gelatin capsule as a commercial product. In addition, higher absorption was observed for S-SNEDDS showing approximately 1.28 and 1.27 fold AUC (0-24h) and Cmax compared to commercial products. Therefore, S-SNEDDS has proven as a novel drug delivery system with a higher drug load, higher self-emulsification efficiency, higher stability, higher dissolution and pronounced absorption.
CONCLUSION: In conclusion, S-SNEDDS could be a newly emerging approach to enhance aqueous solubility in many folds for drugs belonging to BCS Class II and IV and thus absorption and oral bioavailability.

Matched MeSH terms: Dutasteride/chemistry*