Minoxidil Solution Research Articles

Fast determination of minoxidil by photometric flow titration

A photometric flow titration based on the redox reaction between KMnO4 and minoxidil is described. The best titration results were observed at 3.20 x 10-4 mol L-1 KMnO4 and 1.00 x 10-3 mol L-1 minoxidil, using the minoxidil solutions as titrant. The flow rate was fixed at 17 mL min-1 and the titrant was added to the system in aliquots of 500 µL, the color changes were monitored at 550 nm. The method was applied to commercial samples and compared with the results from a chromatographic procedure. Recoveries from 97.6 to 102.8 % were observed depending on the sample. Comparison with the chromatographic procedure reveled relative errors of 3.5 - 4.0 %.

A method for the determination of minoxidil in hair-regrowth formulations by micellar electrokinetic capillary chromatography

A method based on micellar electrokinetic capillary chromatography (MEKC) was developed for determination of minoxidil in Rogaine and competing products. The original intent of the work was to offer an orthogonal means to HPLC for testing illicit imitations of Rogaine. However, because the patent has since expired, we offer the procedure as a confirmatory measure to HPLC for assay of generic minoxidil products. The MEKC procedure complements an earlier method based on free solution capillary electrophoresis (FSCE), designed to the same end. Validation was carried out on both a Dionex CES-1, which utilizes gravity injection, and a PE-ABI 270HT, which employs vacuum injection. The procedure was validated for both active pharmaceutical ingredient and for minoxidil solutions. The run buffer is pH 7.0, 20 mM sodium phosphate, 20 mM sodium dodecyl sulfate, with 10% isopropanol; the internal standard is dl-tryptophan. The method bears the attributes of simplicity, ease of use, and short analysis time (12 min). It is selective with respect to known process and degradation impurities. High efficiency was achieved on the CES-1, with a plate count exceeding 200,000 for minoxidil at an elution time of 9 min. Although slight differences in performance were noted across the two instruments, results on both were in conformance with modern day validation expectations. Comparison of MEKC with HPLC resulted in slightly higher values for the former, but all results met registration specifications and internal targets.

Positive lymphocyte transformation test in a patient with allergic contact dermatitis of the scalp after short‐term use of topical minoxidil solution

Topical 2,4-diamino-6-piperidinopyrimidine-3-oxide (minoxidil) solution has been widely used for the treatment of androgenetic alopecia for over 15 years now and the substance is currently approved for this indication in 2% and 5% formulation. Typical side effects of this topical treatment include irritative dermatitis going along with pruritus, erythema, scaling and dryness, which occur especially at the onset of the therapy. In some cases, allergic contact dermatitis or exacerbation of seborrheic dermatitis has been reported. While most of the patients with allergic contact dermatitis described in the literature showed a positive sensitization to the vehicle substance propylene glycol evaluated by patch testing, reactions to the active ingredient minoxidil are rare. Here, we report a case of allergic sensitization to minoxidil, which we evaluated and differentiated from an irritative reaction by a combination of patch testing and lymphocyte transformation test. The differentiation of allergic and irritative adverse effects and the identification of the causative allergen are of major relevance for the proceeding and adjustment of the therapy. Patients with sensitizations against propylene glycol are candidates for preparations with alternative solvents but can proceed treatment with minoxidil. In contrast, patients with allergies to the active ingredient itself are no longer candidates for treatment with minoxidil and should undergo alternative therapeutic options.

Suspected toxicosis after topical administration of minoxidil in 2 cats

AbstractObjective: To discuss the clinical presentation and necropsy findings of 2 cats after topical administration of a minoxidil solution. Additionally, a potential management plan is offered for future cases.Case summary: Two cats with dermal exposure to topical minoxidil solution were identified from the ASPCA Animal Poison Control Center (APCC) files. Both cats were presented with lethargy and dyspnea within 36 hours of exposure. The cats were hypothermic, and had pulmonary edema and pleural effusion present on thoracic radiography. Both cats died despite supportive care. Necropsy of both cats confirmed pleural effusion and pulmonary edema and indicated cardiac compromise.New or unique information provided: Topical administration of minoxidil solution may cause life‐threatening pulmonary edema, pleural effusion, and cardiac dysfunction in the cat.

An Open, Randomized, Comparative Study of Oral Finasteride and 5% Topical Minoxidil in Male Androgenetic Alopecia

Background and Aim: Androgenetic alopecia (AGA) is undoubtedly the most common form of hair loss in males. It is a condition which may cause cosmetic and psychosocial problems in androgen-dependent cases. In this open, randomized and comparative study we evaluated the efficacy of oral finasteride and 5% topical minoxidil treatment for 12 months in 65 male patients with mild to severe AGA. Methods: We randomly assigned 40 (61.53%) patients to receive 1 mg/day oral finasteride for 12 months, and 25 (38.47%) patients applied 5% topical minoxidil solution twice daily for 12 months. Results: There were no significant differences between the 2 groups considering age, age of onset of hair loss, family history and type of hair loss (p > 0.05). In the clinical evaluation at the endpoint of treatment, the clinical cure rates (i.e. increased intensity of hair) were 80% (32/40) for the oral finasteride group and 52% (13/25) for the 5% topical minoxidil group. Encountered side effects were all mild, and there was no need to stop the treatment. In the group given oral finasteride, side effects were noted in 7 patients: 6 patients suffered from loss of libido, and 1 patient had an increase in other body hairs; irritation of the scalp was seen in 1 patient in the group administered 5% minoxidil. These adverse events disappeared as soon as the treatment was stopped. The laboratory data on both drug groups did not show any statistically or clinically significant intragroup changes from baseline values to the endpoint (p > 0.05), except the level of serum total testosterone which was increased, and free testosterone and serum prostate-specific antigen in the finasteride group which were statistically decreased from baseline values to the endpoint (p < 0.05). Conclusion: In this comparative study of systemic finasteride and topical minoxidil, it was concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although oral finasteride treatment was more effective (p < 0.05). Adverse events were not considered important either, and these side effects disappeared as soon as the treatment was stopped.

A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss

Background To pical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in men with androgenetic alopecia and women with female pattern hair loss. Results can be variable, and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy. Objective The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare the efficacy and safety of 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of female pattern hair loss. Methods A total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. Primary efficacy variables were change in nonvellus hair count at week 48, and patient and investigator assessments of change in hair growth/scalp coverage at week 48. Results After 48 weeks of therapy, 5% topical minoxidil was superior to placebo for each of the 3 primary efficacy measures. The 2% topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. The 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit at week 48. Both 5% and 2% topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss. An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo. Conclusion In this 48-week study of 381 women with female pattern hair loss, 5% topical minoxidil was superior to placebo on each of the 3 primary efficacy end points: promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessments of hair growth and scalp coverage. Application of 2% topical minoxidil was superior to placebo for assessments of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. At week 48, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit. Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects. With the introduction of numerous herbal remedies for hair loss, of which most have not been tested in randomized, double-blind, placebo-controlled trials, it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs.

Alopecia and the Aging Male

Alopecia and the Aging Male

Androgenetic alopecia: combining medical and surgical treatments.

Medical treatment or surgical reconstruction is used separately to treat androgenetic alopecia. Two drug molecules (5% minoxidil solution and oral finasteride 1 mg) have proven efficacy to stabilize hair loss and promote hair regrowth. Microtransplant of one to three hair follicular unit grafts can provide a definitive hair restoration with a natural appearance. Aesthetic results can be optimized with a combination of drugs and transplantation of follicular unit grafts. The Dynamic Multifactorial Classification is used to select suitable candidates for this combined approach and also to assess follow-up results. Dynamic Multifactorial Classification assists the evaluation of the natural history of androgenetic alopecia evolution and also the effects of treatment. Regression of male androgenetic alopecia from Hamilton type V to type III can be achieved by combining drugs with hair grafts. Improvement of investigative methods and especially the Dynamic Multifactorial Classification makes it easier for a patient to follow the results of treatment adapted to their case.

Topical minoxidil counteracts stress-induced hair growth inhibition in mice.

Stress has long been suspected as a possible cause of hair loss in various species, even though convincing experimental evidence has not been available. Recently, we have shown in a murine model that sonic stress alters hair growth and cycling in vivo, and have postulated the existence of a 'brain-hair follicle axis' (BHA). In order to study whether a clinically available and widely used topically active hair growth stimulator mitigates stress-triggered hair growth inhibition in this stress model, we have applied a 5% minoxidil solution. Female CBA/J mice were depilated and randomized in to two groups: control (n = 20) and sonic stress (n = 20). These groups were further divided and either treated daily with 5% minoxidil solution or vehicle alone. The stress group was exposed to sonic stress for 24 h starting 14 days after anagen induction by depilation. All mice were sacrificed 16 days after the depilation and assessed by quantitative histomorphometry. Sonic stress significantly increased the number of hair follicles with apoptotic cells and inhibited intrafollicular keratinocyte proliferation. In addition, the number of clusters of perifollicular MHC class II+ cells and degranulated perifollicular mast cells was significantly enhanced in the stressed mice. In accordance with previous findings, all stressed mice showed an advanced hair cycle progression towards catagen. All of these stress-induced hair growth inhibitory changes along the BHA were down-regulated by topical minoxidil application. This encourages one to explore clinically whether topical minoxidil is a safe and effective pharmacologic tool for the management of stress-associated telogen effluvium in humans.

Safety of topical minoxidil solution: a one-year, prospective, observational study.

Topical minoxidil solution (TMS) is widely used for androgenetic alopecia (AGA), and this is the first report of a large safety trial. The aim of the study was to evaluate the safety profile of TMS by comparing hospitalization and death rates among subjects using TMS with controls. Cardiovascular safety and pregnancy outcomes were evaluated, and usage patterns were described. All subjects were followed at baseline, 3, 6, 9, and 12 months. Usage patterns, pregnancy status, overnight hospital stays, and cardiovascular risk factors were evaluated. Subjects rated effectiveness of TMS in the treatment of AGA. Statistical analyses were conducted to determine if TMS was associated with an increased risk of death or hospitalization. TMS is a safe and effective treatment for AGA. There were no increases in cardiovascular events and no apparent increased risk for adverse pregnancy outcomes. This large, prospective study demonstrated the overall safety of TMS in the treatment of AGA.

Androgenetic alopecia in women.

Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5alpha reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.

The potential role of minoxidil in the hair transplantation setting.

Over the last decade surgical management of hair loss has become an increasingly popular and satisfying procedure for both men and women, as innovations in donor harvesting, graft size, and hairline design have resulted in consistently natural-appearing hair restoration. In addition, a better understanding of the regulation of the hair-growth cycle has led to advances in the pharmacologic treatment of androgenetic alopecia. Currently there are two U.S. Food and Drug Administration (FDA)-approved agents that promote hair regrowth: over-the-counter topical minoxidil solution for men and women and prescription oral finasteride tablets for men. In October 2001, a group of 11 international experts on hair loss and hair transplantation convened to review the physiology and effects of pharmacologic treatments of hair loss and to discuss the value of administering topical minoxidil therapy as an adjunct to hair transplantation. This article presents the key findings and consensus points among the participants, including their current use of pharmacologic treatments, strategies for optimal results both pre- and postsurgery, and the importance of realistic patient expectations and compliance. Based on the surgeons' clinical experience, the use of approved hair regrowth agents in hair transplant patients with viable but suboptimally functioning follicles in the region to be transplanted can increase hair density, speed regrowth in transplanted follicles, and complement the surgical result by slowing down or stopping further hair loss.

A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men

Background: Topical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in individuals with androgenetic alopecia (AGA). Results can be variable, and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy. Objective: The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of men with AGA. Methods: A total of 393 men (18-49 years old) with AGA applied 5% topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by scalp target area hair counts and patient and investigator assessments of change in scalp coverage and benefit of treatment. Results: After 48 weeks of therapy, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in terms of change from baseline in nonvellus hair count, patient rating of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Hair count data indicate that response to treatment occurred earlier with 5% compared with 2% topical minoxidil. Additionally, data from a patient questionnaire on quality of life, global benefit, hair growth, and hair styling demonstrated that 5% topical minoxidil helped improve patients' psychosocial perceptions of hair loss. An increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil. Conclusion: In men with AGA, 5% topical minoxidil was clearly superior to 2% topical minoxidil and placebo in increasing hair regrowth, and the magnitude of its effect was marked (45% more hair regrowth than 2% topical minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier response to treatment than those who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were also improved. Topical minoxidil (5% and 2%) was well tolerated by the men in this trial without evidence of systemic effects. (J Am Acad Dermatol 2002;47:377-85.)

Allergic contact dermatitis to topical minoxidil solution: Etiology and treatment

After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatment for androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen. Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many of these patients may be candidates for treatment with alternative formulations using other solvents, such as butylene glycol, polysorbate, or glycerol. Although predictive, patch testing results do not ensure that the compounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are no longer candidates for topical treatment of their alopecia with any preparations of minoxidil. (J Am Acad Dermatol 2002;46:309-12.)

The treatment of alopecia areata

This article reviews the different treatments of alopecia areata (AA). The information includes both a review of the literature as well as practical aspects regarding the use of the most commonly used therapies for AA. These modalties are summarized in a practical algorithm that can be used as a guide. For patients less than 10 years of age, the options are topical corsticosteroids, topical minoxidil, and anthralin. For adults with less than 50% scalp involvement, the first option is usually the use of intralesional corticosteroids, followed by topical corticosteroid creams, minoxidil solution, or anthralin cream. For adults with more than 50% scalp involvement, topical immunotherapy and phototherapy are added to the other options. Other modalities such as cyclosporine, tacrolimus, interferon, dapsone, and cosmetic coverups are also discussed.

KF19418, a new compound for hair growth promotion in vitro and in vivo mouse models

KF19418, a newly synthesized compound, stimulated proliferation of cultured hair bulb cells from new born mice in concentration-dependent manner in the range under 10 μM. In the culture system of whole skin pieces from 4-week-old mice which we earlier established, KF19418 promoted hair follicle elongation as in the case of minoxidil. After topical application for 2 weeks of KF19418 or minoxidil to dorsal skin of hair-clipped mouse alopecia model, KF19418 at 1% suspension accelerated hair regrowth at a rate comparable to 1% minoxidil solution. Thus, it was shown that KF19418 directly stimulated hair follicle in vitro and had hair growth promoting activities in vivo.

Ethosomes — novel vesicular carriers for enhanced delivery: characterization and skin penetration properties

This work describes a novel carrier for enhanced skin delivery, the ethosomal system, which is composed of phospholipid, ethanol and water. Ethosomal systems were much more efficient at delivering a fluorescent probe to the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solution. The ethosomal system dramatically enhanced the skin permeation of minoxidil in vitro compared with either ethanolic or hydroethanolic solution or phospholipid ethanolic micellar solution of minoxidil. In addition, the transdermal delivery of testosterone from an ethosomal patch was greater both in vitro and in vivo than from commercially available patches. Skin permeation of ethosomal components, ethanol and phospholipid, was demonstrated in diffusion-cell experiments. Ethosomal systems composed of soy phosphatidylcholine 2%, ethanol 30% and water were shown by electron microscopy to contain multilamellar vesicles. 31P-NMR studies confirmed the bilayer configuration of the lipids. Calorimetry and fluorescence measurements suggested that the vesicular bilayers are flexible, having a relatively low T m and fluorescence anisotropy compared with liposomes obtained in the absence of ethanol. Dynamic light scattering measurements indicated that ethanol imparted a negative charge to the vesicles. The average vesicle size, as measured by dynamic light scattering, was modulated by altering the ethosome composition. Experiments using fluorescent probes and ultracentrifugation showed that the ethosomes had a high entrapment capacity for molecules of various lyophilicities.

Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment

Quantitative estimation of hair growth using hair weight and number was recorded for 120 weeks in 4 groups of 9 men with androgenetic alopecia. Three double-blind groups applied either 2% or 5% minoxidil solution, or vehicle. The fourth group, unblinded, received no treatment. Measurements of hair weight and number were continued for 96 weeks, when treatment (if any) was stopped, though measurements were continued for another 24 weeks. Although not compared statistically, the placebo and untreated groups behaved in a similar fashion. In contrast, the 5% and 2% minoxidil treatment groups showed a statistically significant increase in mean percentage change in interval weight from baseline compared with placebo; results for number counts were usually less significant. Over 96 weeks, topical minoxidil induced and maintained an increase in interval weight over baseline of about 30%. After treatment was stopped, hair weight and number counts for the minoxidil groups returned to about the same levels as placebo in 24 weeks. (J Am Acad Dermatol 1999;41:717-21.)

The induction by topical minoxidil of increased fenestration in the perifollicular capillary wall.

We report the induction by topical minoxidil of increased fenestration in the perifollicular capillary wall. Male 30-day-old Wistar rats were divided into two groups, i.e. an experimental group which received 4% minoxidil solution topically on the dorsal skin, and a control group which received only vehicle solution topically. Using transmission electron microscopy, follicular and subepidermal capillaries and dermal fibres were compared between both groups. There were no obvious differences in subepidermal capillaries or dermal fibres between the two groups. However, topically applied minoxidil increased fenestration in follicular capillary walls around anagen hair bulbs.

HPLC determination of the stability of tretinoin in tretinoin–minoxidil solution

A new formulation of topical tretinoin–minoxidil solution was prepared and the chemical stability of tretinoin was studied for 6 months at 4°C. A reversed phase high performance liquid chromatography (HPLC) method was developed for determination of tretinoin using cyanocobalamine as an internal standard. Tretinoin was shown that to be stable for at least 6 months used refrigerated storage conditions.