Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target.

Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of finasteride on phenylethanolamine N-methyltransferase (PNMT), the limiting enzyme in formation of the stress hormone epinephrine. The interaction of finasteride with PNMT was supported by docking and molecular dynamics analysis and by in vitro assay, confirming the inhibitory nature of the binding. Finally, this inhibition was also confirmed in an in vivo rat model. Literature data indicate that PNMT activity perturbation may be correlated with sexual and psychological side effects. Therefore, results here obtained suggest that the binding of finasteride to PNMT might have a role in producing the side effects exerted by finasteride treatment.

Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride.

Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme in steroid metabolism and catalyzes the reduction of testosterone to dihydrotestosterone. Mutations in the SRD5A2 gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. The molecular mechanisms underlying enzyme catalysis and inhibition for SRD5A2 and other eukaryotic integral membrane steroid reductases remain elusive due to a lack of structural information. Here, we report a crystal structure of human SRD5A2 at 2.8 Å, revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region that regulate NADPH/NADP+ exchange. Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and may facilitate drug development.

Water-stable and finasteride-loaded polyvinyl alcohol nanofibrous particles with sustained drug release for improved prostatic artery embolization - In vitro and in vivo evaluation.

Prostatic artery embolization (PAE) has been a well-established treatment for benign prostatic hyperplasia (BPH). To enhance the therapeutic efficacy, a strategy is to use embolic agent preloaded with 5α-reductase inhibitors for localized drug delivery. In this study, finasteride (FNS) was encapsulated into the polyvinyl alcohol (PVA) nanofibers via co-electrospinning technique, followed by heat treatment and cryogenic grinding to convert them into nanofibrous particles as a drug-loaded embolic agent. The FNS was found to be distributed uniformly in PVA nanofibers, and the processed FNS/PVA nanofibrous particles were 272 µm in mean particle size. Besides, the studies on the composition, thermal properties, swelling ratio, and water stability of the nanofibers and drug showed that the FNS remained its crystalline state in PVA nanofibers. The heat treatment increased the crystallinity of nanofibers and rendered them water stability. Both FNS and PVA possessed excellent thermal stability at high temperature (150 °C). In addition, in vitro drug release studies suggested the FNS followed a favorable sustained release up to 744 h. Furthermore, the cell viability and hemocompatibility assays indicated the nanofibers possessed excellent cytocompatibility and with no evidence of hemolysis. More importantly, the in vivo PAE procedures on beagles demonstrated the crosslinked FNS/PVA nanofibrous particles exhibited higher embolization efficacy with more obvious prostate volume (PV) reduction compared to crosslinked PVA nanofibrous particles after embolization for 1, 3, and 6 months (P < 0.05). Therefore, such drug-loaded PVA nanofibrous particles combined physical embolization and localized medical therapy together, which offer great potential to be used as an effective embolic agent for BPH therapy.

Finasteride and Its Potential for the Treatment of Female Pattern Hair Loss: Evidence to Date.

The currently approved treatment for female pattern hair loss (FPHL) includes topical minoxidil administration; however, this treatment fails to achieve hair regrowth in some patients. Finasteride, a selective 5α-reductase inhibitor (5-ARI), may be considered as an alternative treatment. However, because of its potential teratogenic effects, clinical studies and use of finasteride for FPHL are limited. In this review, we aim to summarize the literature regarding the pharmacology, clinical efficacy, and adverse effects of oral finasteride for the treatment of FPHL and to provide novel therapeutic options including topical finasteride and dutasteride, a new generation 5-ARI, for the treatment of FPHL.

Development of finasteride/PHBV@polyvinyl alcohol/chitosan reservoir-type microspheres as a potential embolic agent: from in vitro evaluation to animal study.

Benign prostatic hyperplasia (BPH) is a prevalent urological disease affecting elders. Currently, the prostatic artery embolization (PAE) is considered as a minimally invasive and safe technique to treat BPH. However, various drug-loaded embolic agents have not been thoroughly investigated in BPH therapy. In this study, finasteride/poly(3-hydroxybutyrate-3-hydroxyvalerate)@polyvinyl alcohol/chitosan (FNS/PHBV@PVA/CS) reservoir-type microspheres were prepared via the solid-in-water-in-oil (S/W/O) emulsion crosslinking method with the aim to reduce the burst effect and control localized drug delivery. The structure and properties of the drug and resultant microspheres were characterized via field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the drug-loaded hybrid microspheres were well-dispersed and spherical with a mean diameter of 238.1 ± 27.3 µm. All samples exhibited excellent thermal stability. The FNS/PHBV microspheres were successfully encapsulated inside the PVA/CS polymeric matrix, which effectively suppressed the burst effect and prolonged the drug release up to 51 days. In vitro biocompatibility assessment indicated that the microspheres possessed excellent cytocompatibility and hemocompatibility. Furthermore, in vivo studies performed in the rabbit ear embolization model showed the formation of progressive ischemic necrosis after treatment for various periods. Histopathological studies revealed that the microspheres completely occluded the blood vessels with minimal foreign body response and formed the fibrotic area at the periphery of embolized arteries. Furthermore, the auricular vascular endothelial cells showed acute ultrastructural changes, associated with the ischemic necrosis induced by the embolization procedures. All these findings suggest that the FNS/PHBV@PVA/CS hybrid microspheres could be used as a promising drug delivery system for potential applications in BPH therapy.

Quintaquinone, a Merosesquiterpene from the Yellow Sponge Verongula cf. rigida Esper.

A chemical investigation of the sponge Verongula cf. rigida led to the isolation of 13 merosesquiterpenes, among which quintaquinone (2), 5-epi-nakijiquinone L (3), and 3-farnesyl-2-hydroxy-5-methoxyquinone (4) were isolated and reported here for the first time. Particularly, compound 2 is the first member of merosesquiterpenes with a polyketide side chain substituted on C-19. All of the isolated compounds were examined for steroid 5α-reductase inhibitory activity. Cyclospongiaquinone 1 (5) showed a strong activity in the same range as that of standard finasteride.

Preformulation studies of finasteride to design matrix systems for topical delivery.

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-ß-cyclodextrin (HPßCD) 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 HPßCD, 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.

Preparation, Optimization, In vitro Evaluation and Ex vivo Permeation Studies of Finasteride loaded gel Formulations Prepared by using Response Surface Methodology.

OBJECTIVES: The aim of the present explorative study was to prepare and optimize finasteride loaded topical gel formulations by using three factor [propylene glycol (PG), Tween® 80, and sodium lauryl sulphate (SLS)], five level central composite design. RESULTS: Optimized finasteride topical gel formulation (F4), containing PG, Tween® 80, and SLS in a concentration of 0.8 mg, 0.4 mg and 0.2 mg, respectively, showed 6-fold higher values of cumulative drug release, flux, partition coefficient, input rate, lag time, and diffusion coefficient, when compared to control formulation without permeation enhancer. CONCLUSION: Finally, it can be concluded that finasteride permeation was enhanced by PG, tween® 80 and SLS individually, while in combination only PG along with tween® 80 had synergistic and more pronounced effect on flux, permeability coefficient and input rate while antagonistic effect on lag time and diffusion coefficient was observed.

Stability Study of Finasteride: Stability-Indicating LC Method, In Silico and LC-ESI-MS Analysis of Major Degradation Product, and an In Vitro Biological Safety Study.

Stability studies of the pharmaceutically important compound finasteride were conducted in order to evaluate decomposition of the drug under forced degradation conditions. A simple stability-indicating liquid chromatography method was developed and validated for the evaluation of finasteride and degradation products formed in pharmaceutical preparations and the raw material. Isocratic LC separation was achieved on a C18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile (52:48 v/v), with a flow rate of 1.0 mL min-1. The alkaline degradation kinetics of the drug were also evaluated and could be best described as second-order kinetics under the experimental conditions applied for the tablets and raw material. Based on in silico studies and molecular weight confirmation, a comprehensive degradation pathway for the drug and the identity of its major product could be suggested without complicated isolation or purification processes. Furthermore, a biological safety study was performed to evaluate the effect of the degraded sample in relation to the intact molecule. The results showed that the degraded sample affected the cell proliferation. Therefore, these studies show that special care must be taken during the manipulation, manufacture and storage of this pharmaceutical drug.

Determination of finasteride and its metabolite in urine by dispersive liquid-liquid microextraction combined with field-enhanced sample stacking and sweeping.

The on-line preconcentration technique of field-enhanced sample stacking and sweeping (FESS-sweeping) are combined with dispersive liquid-liquid microextraction (DLLME) to monitor the concentrations of finasteride, which is used in the treatment of androgenetic alopecia, and its metabolite, finasteride carboxylic acid (M3), in urine samples. DLLME is used to concentrate and eliminate the interferences of urine samples and uses chloroform as an extracting solvent and acetonitrile as a disperser solvent. A high conductivity buffer (HCB) was introduced into capillary and then sample plug (90.7% capillary length) was injected into capillary. After applying voltage, the sodium dodecyl sulfate (SDS) swept the analytes from the low conductivity sample solution into HCB. The analytes were concentrated on the field-enhanced sample stacking boundary. The limit of detection for the analytes is 20 ng mL-1. The sensitivity enrichment of finasteride and M3 are 362-fold and 480-fold, respectively, compared with the conventional MEKC method. The on-line preconcentration technique of field-enhanced sample stacking and sweeping possess good selectivity because the endogenous steroid did not interfere the detection of finasteride and M3. The analytical technique is applied to investigate the concentrations in urine samples from patients who have been administered finasteride for the treatment of androgenetic alopecia; the amount of M3 detected in 12 h was 72.69 ±â€¯4.18 µg.

Imaging prostate cancer (PCa) with [99m Tc(CO)3 ]finasteride dithiocarbamate.

This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net4 ]2 [ReBr3 (CO)3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[99m Tc(H2 O)3 (CO)3 ]+ precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa.

Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit.

Androgenetic alopecia, a major cause for baldness, is caused by the deposition of dihydrotestosterone (DHT) at the androgen receptors present in the pilosebaceous unit (PSU). Finasteride (FIN) is a potent 5α-reductase inhibitor capable of preventing the conversion of testosterone to DHT. But, its oral administration in males causes infertility. An attempt was made to prepare ethosomes of FIN with a size range 100-300 nm to enhance its delivery to the PSU. Finasteride loaded ethosomes (FES) were prepared using an ultra-probe sonicator and characterized for its size, morphology, surface charge and entrapment efficiency. The ability of FES to permeate across rat skin and frontal scalp skin of human cadaver was also evaluated. The spherical shaped ethosomes of different batches were in the size range of 107.8 ± 2.50 to 220.4 ± 6.92 nm and showed good permeation across rat skin and frontal scalp skin of human cadaver when compared to the unencapsulated FIN. The results portrayed the ability of FES to permeate across the stratum corneum to reach the PSU of the hair follicle. Although additional use of permeation enhancer increases the permeation of FIN across the skin, its addition may not be a favourable option for the deposition of ethosomes in the PSU.

Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior.

OBJECTIVE: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS). SIGNIFICANCE: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia. METHODS: Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers. RESULTS: Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product. CONCLUSION: Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems.

Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia.

BACKGROUND/AIMS: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. METHODS: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. RESULTS AND CONCLUSIONS: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.

Experimental, molecular docking investigations and bioavailability study on the inclusion complexes of finasteride and cyclodextrins.

Finasteride (FIN) is a Class II candidate of the Biopharmaceutics Classification System (BCS). The lipophilic cavity of cyclodextrins (CyDs) enables it to construct a non-covalent inclusion complex with different insoluble drugs. Only ß-cyclodextrin (ß-CyD) and hydroxypropyl-ß-CyD (HP-ß-CyD) have been previously examined with FIN. This study aimed to investigate the consistence of FIN with different kinds of ß-CyDs, including dimethyl-ß-cyclodextrin (DM-ß-CyD), carboxymethyl-ß-cyclodextrin (CM-ß-CyD), HP-ß-CyD, sulfobutyl ether-ß-cyclodextrin (SBE-ß-CyD), and ß-CyD, by the coprecipitation method. The resultant inclusion systems were characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffractometry, and dissolution studies. Moreover, molecular docking for the selected inclusion systems was carried out to explore the suitable arrangements of FIN in the cavity of ß-CyD or its derivatives. The results suggested that the DM-ß-CyD inclusion system gave the higher complexation efficiency for improvement in solubility of FIN and hence enhancement of its bioavailability. Pharmacokinetic parameters displayed a higher absorption rate and higher area under the curve of the FIN/DM-ß-CyD inclusion complex when compared with the drug alone, which indicates an improvement in the absorption and bioavailability of FIN in the DM-ß-CyD inclusion system.

Effects of testosterone on mean arterial pressure and aquaporin (AQP)-1, 2, 3, 4, 6 and 7 expressions in the kidney of orchidectomized, adult male Sprague-Dawley rats.

We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys. METHODS: Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 µg/kg/day or 250 µg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence. RESULTS: Testosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p < 0.05). AQP-1 and 7 were found to be distributed in the proximal convoluted tubule (PCT) while AQP-2, 3, 4 and 6 were found to be distributed in the collecting ducts (CD). Effects of testosterone were antagonized by flutamide and finasteride. CONCLUSIONS: Elevated expression of AQP-1, 2, 4, 6 and 7 under testosterone influence in kidneys could lead to increase H2O reabsorption which eventually lead to increase in blood pressure.

Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study.

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.

Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation.

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom-up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.

Self-microemulsifying systems of Finasteride with enhanced oral bioavailability: multivariate statistical evaluation, characterization, spray-drying and in vivo studies in human volunteers.

AIM: To develop Finasteride-loaded self micro-emulsifying drug delivery systems (SMEDDS) for the treatment of hormonal associated problems. MATERIALS & METHODS: Ternary phase diagrams were constructed to obtain self-emulsification regions. Multivariate statistical methods viz. Principal component analysis and agglomerative hierarchy clustering analysis were used to evaluate the microemulsions stability. In vitro redispersibility study was adopted and two formulations were selected for spray-drying. Further investigations were performed (Fourier transform infrared, x-ray diffraction and transmission electron microscopy). Finally, the in vivo performance was tested in human volunteers. RESULTS: Multivariate statistical methods selected stable SMEDDS. Spray-drying utilizing maltodextrin/leucin carrier system yielded a flowable product. Selected solid SMEDDS scored 129.35% relative bioavailability compared with a commercial tablet. CONCLUSION: The developed SMEDDS poses successful platform for glucosteroid analogs oral delivery.