In view of the fact that the oral administration of finasteride (FIN) has resulted in various undesirable systemic side effects, the topical application of polystyrene and poly(acrylic acid)-based ...polymersomes (underexplored system) was investigated. Undecorated PS139-b-PAA17 and PS404-b-PAA63 vesicles (C3 and C7, respectively) or vesicles decorated with chitosan samples of different molecular weight (C3/CS-oligo, C7/CS-oligo, C3/CS-37 and C7/CS-37) were prepared by the co-solvent self-assembly method and characterized by small-angle X-ray scattering,transmission electron microscopy and dynamic light scattering techniques. In vitro release experiments and ex vivo permeation using Franz diffusion cells were carried out (through comparison with hydroethanolic finasteride solution). The ideal system should provide high finasteride retention in the dermis and epidermis while allowing some control of the drug release. The particle size and in vitro release were negatively correlated with the permeation coefficient and skin retention in both the epidermis and dermis. The findings that the longest lag time was obtained for the hydroethanolic drug solution and lowest permeation for the systems able to release the drug faster support the hypothesis that nanostructured systems may be required to enhance the penetration and permeation of the drug. Chitosan-decorated polymersomes interacted more strongly with the skin components than non-decorated samples, probably due to the positive surface charge, which increased the FIN retention and reduced the lag time. C7 polymersomes decorated with chitosan were more appropriate for topical applications (high retention in the dermis and epidermis and controlled drug delivery).
The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in ...gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box–Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93μm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1–Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films.
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Purpose
5-alpha reductase inhibitor (5ARI) reduces prostate-specific antigen (PSA) by half but its effect on prostate health index (
phi
) is unknown. This study aims to investigate this effect and ...to enable accurate interpretation of
phi
in men with elevated PSA and on 5ARI.
Methods
This is a prospective study evaluating the effect of finasteride on PSA, free PSA (fPSA), – 2proPSA (p2PSA) and
phi
at 6 and 12 moths in men with PSA 4-20 ng/mL, no prior 5ARI use, and one negative prostate biopsy within 6 months before recruitment. The 5ARI Finasteride (5 mg/day) for 1 year was offered if International Prostatic Symptom Score (IPSS) was ≥ 8 at baseline. 5ARI group included patients taking finasteride, while control group included patients not on finasteride. The blood results were compared with
t
-test between baseline and different time points in each group and between groups at 1 year.
Results
164 men fit the inclusion criteria and 150 were analyzed. In 5ARI group (n = 100) at 1 year, mean PSA reduced by 51.4% from 8.9(± SD 3.7) to 4.4(± SD 2.8)ng/mL (paired t-test, p < 0.001), fPSA reduced by 52.4% from 1.6(± 0.6) to 0.8(± 0.4)ng/mL (p < 0.001), p2PSA reduced by 55.3% from 18.4(± 8.8) to 8.3(± 5.6)pg/mL (p < 0.001), and
phi
reduced by 34.2% from 33.7(± 11.9) to 22.4(± 12.5) (p < 0.001). PSA and
phi
values in the control group remained static over 1 year and significantly higher than those in 5ARI group.
Conclusion
This study demonstrated p2PSA and phi are reduced by about 55% and 34% in men on 5ARI. A conversion factor of division by 0.66 is needed for
phi
in men on finasteride to allow the interpretation and use of
phi
in men on 5ARI.
Pediatric androgenetic alopecia: A review Griggs, Jacob; Burroway, Brandon; Tosti, Antonella
Journal of the American Academy of Dermatology,
November 2021, 2021-11-00, 20211101, Letnik:
85, Številka:
5
Journal Article
Recenzirano
Androgenetic alopecia (AGA) is a well-known cause of hair loss in adults but is an under-recognized cause of hair loss in children and adolescents. We reviewed the existing literature regarding ...androgenetic alopecia in the pediatric/adolescent population.
PubMed searches were performed to identify all articles discussing AGA in a pediatric/adolescent population published up to December 2018.
We identified 7 articles discussing androgenetic alopecia in patients aged younger than 18. One of these articles was a review containing data from 3 conference abstracts, which were also included in the analysis. A total of 655 cases of androgenetic alopecia were found.
Data are limited to retrospective reviews and case reports/series.
AGA in the pediatric population is not uncommon, but its incidence and prevalence are unknown. It is associated with a strong family history of AGA and can typically be diagnosed clinically by physical examination and trichoscopy. Topical minoxidil, although not approved, has been used with success. Other treatment modalities are poorly studied in children.
The current work aimed to formulate a novel chitosan-based finasteride nanosystem (FNS-NS) for skin delivery to optimize the drug availability in skin for a longer time and enhance ex vivo ...performance of finasteride against androgenic alopecia.
Both undecorated and chitosan decorated FNS-NSs were synthesized by a high energy emulsification technique. All the prepared nanosystems were further subjected to physicochemical characterizations like pH, viscosity, encapsulation efficiency, surface morphology and in vitro drug release behavior. The influence of the nanosystem on the drug permeation and retention in rat skin was examined using Franz diffusion cell apparatus.
The droplet size of developed nanosystems ranged from 41 to 864 nm with a low polydispersity index. The zeta potential of the nanosystems was between -10 mV and +56 mV. This chitosan decorated nanosystem exhibited controlled drug release, ie about 78-97% in 24 h. Among all the nanosystems, our chitosan decorated formulation (F5) had low drug permeation (16.35 µg/cm
) and higher drug retention (10.81 µg/cm
).
The abovementioned results demonstrate satisfactory in vitro drug release, skin retention profiles and ex vivo performance with chitosan decorated FNS-NS (F5). This optimized formulation could increase drug availability in skin and could become a promising carrier for topical delivery to treat androgenic alopecia.
Abstract
Pattern hair loss (PHL) is a condition that worsens with time and the only way it can be slowed down is with pharmacological intervention. Pharmacological treatments for PHL, from an ...evidenced-based perspective with respect to safety and efficacy, are limited to only two drugs, minoxidil and finasteride. However, there are a host of drugs being used, off-label with limited evidence. This article attempts to review the literature on this topic, and the authors add to this, with their experience of over two decades on incorporating pharmacologic treatments along with hair transplantation in their management of PHL.
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In our previous study, a long-acting injectable (LAI) formulation of finasteride was prepared as a new dosage form of PROPECIA®, and in vivo pharmacokinetics (PKs)-pharmacodynamics ...(PDs) was evaluated in beagle dogs. The resulting PK-PD profiles of the formulation showed pharmacological effects and achievability for monthly delivery. In this study, a first-in-human (FIH) dose of the LAI formulation loaded with finasteride was predicted. The three approaches were used for estimating a FIH dose of the LAI formulation: (1) No observed adverse effect level (NOAEL)-based approach; (2) Pharmacokinetically-guided approach; (3) Pharmacokinetic/pharmacodynamic model-based approach. The advantage, assumptions, limitations, and estimated FIH dose from each approach was discussed and compared since there is no consensus on the best approach. For the prediction of clinical exposures and estimation of FIH doses, the clinical PK-PD parameters were allometrically scaled from the nonclinical data, extracted from reported clinical studies, or fixed from published literature. The starting dose range of the LAI formulation (as finasteride) was estimated to be 16.80–81.06 mg from the three approaches, and the PK/PD model-based approach suggests the most optimal starting dose (16.80 mg) of the LAI formulation. The approaches for estimating starting doses presented in the study could be used as a basis for an Investigational New Drug (IND) application of new dosage forms.
Purpose
The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations ...of heat and use of specific chemical penetration enhancers.
Methods
Franz cell experiments with human scalp skin were performed with a range of chemical penetration enhancers at 32°C and 45°C to simulate normal and heated conditions. Selected chemical penetration enhancers were taken forward for finite dose Franz cell studies which examined the effect of heat produced by a prototype external heating system that supplied either 20 or 30 min of additional heat over both a 24 h and a 1 h time period.
Results
Short durations of externally applied heat significantly increased finasteride penetration into human scalp skin after 24 h. Analysis of drug distribution in the skin after 1 h and 24 h indicated that both heat and chemical penetration enhancer selection influenced drug delivery to the hair follicles.
Conclusion
The use of short durations of heat in combination with specific chemical penetration enhancers was able to increase the delivery of finasteride to human scalp skin and provide focussed drug delivery to the hair follicles.
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•Preformulation of finasteride was performed using a simplex centroid mixture design.•Drug interaction with polymers and cyclodextrin were identified by thermal ...analysis.•Hydroxypropyl cellulose facilitated cyclodextrin-drug inclusion complex formation.•Chemical stability of the different mixtures was preserved after thermal treatment.•Interaction with excipients suggest s a stabilization of the original drug crystalline phase.
A preformulation study with finasteride (FIN) was conducted to enable the development of a topical matrix system to treat androgenic alopecia. The compatibility of the drug with hidroxypropyl-β-cyclodextrin (HPβCD) and the hydrophilic polymers Klucel EXF (KLU) and Soluplus (SOL) were evaluated according to a simplex centroid mixture design. An extensive analytical arsenal was used to encompass the stability of the drug in the different mixtures. The selected excipients showed to have intense thermal interaction with FIN, which was dependent on the composition of the sample, shifting FIN melting peak to reduced temperatures along with the decrease of its associated enthalpy. The mixture design allowed measuring the interactions between components, showing that KLU enhanced the ability of the drug to form inclusion complexes with HPβCD, while SOL exhibited the opposite effect. The stability of samples was preserved even after a thermal treatment used to simulate pharmaceutical processing. Indeed, no drug content decaying was observed, which corroborates the chemical stability of the systems as indicated by thermogravimetry, chromatographic, morphological and spectroscopic assays. The original crystalline phase of the drug (orthorhombic form I) did not change after the heating treatment of the samples, demonstrating its physical stability. Thus, these series of experiments may guide the development of delivery systems for topical use of FIN, showing which combinations and proportions of components can lead to better results in terms of stability and drug delivery.