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.     

Development and validation of a procedure for the determination of minoxidil in hair-regrowth formulations using two variants of capillary zone electrophoresis

A high performance capillary electrophoresis method was developed and validated for purity assessment of minoxidil bulk drug and for determination of minoxidil in Rogaine. The principal use of the method was in analyzing illicit minoxidil-containing hair-regrowth samples. Although validated for Rogaine, the procedure proved equally viable on illicit minoxidil-containing preparations. The developed method fulfilled the goal of providing an orthogonal technique to HPLC for confirmation of the presence of minoxidil in these imitations. The method was validated on two instruments, one utilizing EK injection, the other gravity injection. It is selective for minoxidil, which is separated from known process impurities and the single degradation impurity. Validation figures of merit for linearity/recovery (accuracy) and precision were in accordance with current expectations for method validation.     

Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil

Minoxidil is widely used for treatment of androgenic alopecia. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness. The aims of this study were to prepare lecithin-based microparticle in minoxidil solution for enhancement of minoxidil topical delivery and skin protection and evaluate the ability of lecithin on in vitro delivery, in vivo hair growth, and skin trouble improvement compared to commercial minoxidil solution. In in vitro skin permeation study, minoxidil solution containing lecithin microparticle showed higher skin penetration rate and higher retention of drug inside the skin compared to minoxidil solution without lecithin. After topical application of minoxidil solutions with or without lecithin to C57BL/6 mice, minoxidil 5% solution containing lecithin microparticle showed hair re-growth as efficient as commercial product of minoxidil 5% solution. It also significantly improved skin troubles while commercial product presented horny substance and crust formation. Therefore, the lecithin-based microparticle in minoxidil 5% solution has good ability to promote hair growth without adverse effects.     

Effect of Citrullus colocynthis. on Hair Growth in Albino Rats

Abstract

Citrullus colocynthis. Schrad (Cucurbitaceae) is a traditionally acclaimed hair tonic in Ayurveda (the traditional Indian system of medicine). Studies were therefore undertaken to evaluate petroleum ether and ethanol extracts of C. colocynthis. for their effect on hair growth in albino rats. The extracts incorporated into oleaginous ointment base were applied topically on shaved denuded skin of albino rats. The time required for initiation of hair growth as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as the standard. Hair growth initiation time was significantly reduced to half on treatment with the petroleum ether extracts compared with untreated control animals. The time required for complete hair growth was also considerably reduced. The treatment was successful in bringing a greater number of hair follicles (>70%) to anagenic phase than standard minoxidil (67%). The result of treatment with 2 and 5% petroleum ether extracts were comparable with the standard minoxidil.     

米诺地尔醇脂质体的制备

目的制备米诺地尔醇脂质体并评价其质量。方法采用乙醇注入法制备米诺地尔醇脂质体,以包封率为评价指标进行正交试验筛选出最佳的处方和工艺。采用HPLC测定主药含量、透析袋法测定醇脂质体的包封率。并对其粒径、电位、包封率等理化性质进行研究。结果各因素最佳的水平组合：药脂重量比为1∶10、胆固醇与大豆磷脂的重量比为1∶2、无水乙醇为处方量的30%。所制醇脂质体为乳黄色,平均粒径为1.103μm,Zeta电位为-3.69 mV,平均包封率为66.7%。结论米诺地尔醇脂质体的制备工艺简便可行,质量稳定可控,为开发新剂型奠定了实验基础。     

Predictors of non-fatal overdose among a cohort of polysubstance-using injection drug users

BACKGROUND: Non-fatal overdose is a major determinant of morbidity among injection drug users (IDU). We sought to evaluate factors associated with non-fatal overdose among IDU in Vancouver. METHODS: We examined non-fatal overdose among participants in the Vancouver Injection Drug Users Study. Correlates of non-fatal overdose occurring between 1996 and 2004 were identified using generalized estimating equations (GEE). RESULTS: There were 1587 participants included in this analysis, including 576 (36%) women. At baseline, 750 (47%) reported a history of non-fatal overdose. In total, 985 reports of non-fatal overdose were made during follow-up by 519 (32.7%) participants. In multivariate GEE analyses, factors independently associated with non-fatal overdose included: heroin injection (AOR=2.67), cocaine injection (AOR=2.01), benzodiazepine use (AOR=2.00), requiring help injecting (AOR=1.58), binge drug use (AOR=1.52), homelessness (AOR=1.38), alcohol use (AOR=1.32), street injecting (AOR=1.22), non-injectable opiate use (AOR=1.16), speedball use (AOR=1.15), and recent incarceration (AOR=1.14). Younger age (AOR=0.99) and methadone use (AOR=0.51) were protective. CONCLUSIONS: We found that non-fatal overdose was common among local IDU. Non-fatal overdose was associated with several factors that may be amenable to intervention, including opiate and stimulant use, and the characteristic of requiring help with injecting. These findings indicate the need for the ongoing development of structural interventions to address this common cause of morbidity among IDU.     

Relationship between contact time of applied dose and percutaneous absorption of minoxidil from a topical solution

Twenty-two healthy male volunteers completed a four-way, multiple-dose, randomized crossover study to determine the relationship between contact time of applied drug on the scalp and minoxidil absorption from a 2% topical solution. One milliliter of solution was applied twice daily over 150 cm2 of bald scalp to each subject for 6 days. Unabsorbed drug was washed off the scalp after 1, 2, 4, and 11.5 h of contact time in each of four treatments. Cumulative urinary excretion profiles within steady-state, 12-h dosing intervals were well described by straight lines for all treatments, indicating that systemic minoxidil elimination was rate controlled by constant, zero-order percutaneous drug absorption. The extent of minoxidil absorption, expressed as steady-state urinary excretion of unchanged minoxidil, minoxidil glucuronide, or the sum of these, increased in a disproportionate manner with increase in contact time of drug on the scalp. Relative to the amount absorbed after a contact time of 11.5 h, absorption was approximately 50% complete by 1 h and greater than 75% complete by 4 h. This suggests that minoxidil absorption from the vehicle into skin occurs rapidly relative to diffusion through skin. The rate of minoxidil absorption from vehicle into skin was characterized as nonlinear, whereas minoxidil excretion into urine was rate controlled by diffusion from one or more components of the skin which apparently serve as a reservoir, or depot, for minoxidil.     

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning.

PURPOSE: The efficacy, safety, and cost issues that should be considered when deciding on the appropriate route of acetylcysteine for the treatment of patients with acetaminophen poisoning are reviewed. SUMMARY: Oral and i.v. acetylcysteine appear to be equally effective when given within 8-10 hours of acetaminophen overdose. Anaphylactoid reactions to i.v. acetylcysteine have generally been reported in 3-6% of acetaminophen-poisoned patients. Dosing errors and hyponatremia have occurred in pediatric patients receiving i.v. acetylcysteine. Several investigators found an increased rate of anaphylactoid reactions in patients treated with i.v. acetylcysteine whose pretreatment serum acetaminophen levels were nontoxic. Compounding i.v. acetylcysteine from the oral preparation is less expensive than using premade i.v. solution. State pharmacy laws dictate whether extemporaneous compounding of acetylcysteine from the oral formulation is allowed. Oral acetylcysteine administration has resulted in minimal anaphylactoid reactions and is safer than i.v. acetylcysteine. Oral therapy should preferentially be considered in patients with asthma or atopic histories. The most important factors to consider when selecting the route of acetylcysteine administration include individual susceptibility, the severity of acetaminophen toxicity, and the time interval between acetaminophen ingestion and initiation of acetylcysteine therapy. CONCLUSION: Oral acetylcysteine administered within 8-10 hours of acetaminophen overdose prevents liver toxicity in the majority of patients who tolerate it and have no contraindications to therapy. I.V. acetylcysteine should be administered when patients are treated more than 10 hours postingestion of acetaminophen overdose or have underlying conditions preventing oral treatment. Anaphylactoid reactions are rare and occur more frequently in patients treated with the i.v. preparation.     

Topical minoxidil: cardiac effects in bald man.

Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy.     

Non-fatal overdose and subsequent drug treatment among injection drug users

Overdose is a leading cause of death among illicit drug users. Nine hundred twenty-four injection drug users (IDUs) in Baltimore, Maryland, were interviewed to characterize overdose events and determine the circumstances under which they lead to drug treatment. Overall, 366 (39.7%) reported at least one non-fatal drug overdose. Most (96.2%) used heroin on the day of their last overdose and almost half (42.6%) used heroin and alcohol but few (4.1%) used tranquilizers or benzodiazepines. Five percent were in drug treatment when the overdose occurred and 7.1% had been incarcerated 2 weeks prior. One in four IDUs (26.2%) sought drug treatment within 30 days after their last overdose of whom 75% enrolled. Speaking with someone about drug treatment after the overdose was associated with treatment seeking (AOR 5.22; 95% CI: 3.12, 8.71). Family members were the most commonly cited source of treatment information (53.7%) but only those who spoke with spouses, crisis counselors and hospital staff were more likely to seek treatment. Not being ready for treatment (69.6%) and not viewing drug use as a problem (30.7%) were the most common reasons for not seeking treatment and being placed on a waiting list was the most common reason for not subsequently enrolling in treatment (66.7%). Of the IDUs treated by emergency medical technicians, ER staff or hospital staff, only 17.3%, 26.2% and 43.2% reported getting drug treatment information from those sources, respectively. Interventions that provide drug treatment information and enhance motivation for treatment in the medical setting and policies that reduce barriers to treatment entry among motivated drug users are recommended.     

Induction of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by triamcinolone acetonide: impact on minoxidil-mediated hypotension

The hypotensive agent minoxidil (6-imino-1, 2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine) depends upon aryl sulfotransferase (SULT1)-catalyzed sulfation for its bioactivation. Previous reports suggest that glucocorticoids induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocorticoid triamcinolone acetonide (TA, 5 mg/kg/day i.p. x 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pressure (MAP), heart rate (HR), and hepatic SULT1 gene expression were characterized. Minoxidil treatment (1.5 mg/kg) resulted in a steady decline in MAP values of 16.3 to 18.6% relative to basal control levels at 35 to 60 min following minoxidil injection. Pentachlorophenol (PCP, 40 micromol/kg i.p.), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive effects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-treated rats displayed a steeper rate of decline in MAP and more profound levels of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA expression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), relative to vehicle-treated controls. These results provide physiological evidence to support the biological relevance of SULT1A1 induction by glucocorticoids. The data indicate that steroid treatment induces SULT1A1 gene expression and, as a consequence, accentuates the hypotensive effects of minoxidil.     

Heroin overdose among young injection drug users in San Francisco

OBJECTIVES: We sought to identify prevalence and predictors of heroin-related overdose among young injection drug users (IDU). METHODS: A total of 795 IDU under age of 30 years were interviewed in four neighbourhoods in San Francisco, California, USA. Participants were recruited as part of a broader study of HIV, hepatitis B and C among injecting drug users in San Francisco using street outreach and snowball techniques. Independent predictors of recent heroin overdose requiring intervention were determined using regression analysis. RESULTS: Of 795 injecting drug users under age of 30 years, 22% (174/795) of participants reported a heroin overdose in the last year. In stepwise multiple logistic regression, independent predictors of recent heroin overdose were lifetime incarceration exceeding 20 months (odds ratio (OR) = 2.99, 95% confidence interval (CI) = 1.52-5.88); heroin injection in the last 3 months (OR = 4.89, 95% CI = 2.03-11.74); cocaine injection in the last 3 months (OR = 1.67, 95% CI = 1.14-2.45); injection of heroin mixed with methamphetamine in the last 3 months (OR = 1.74, 95% CI = 1.15-2.65); ever tested for hepatitis B or C (OR = 1.66 per year, CI = 1.09-2.54) and ever having witnessed another person overdose (OR = 2.89, 95% CI = 1.76-4.73). CONCLUSIONS: Individuals with high levels of incarceration are at great risk of overdose, and prison or jail should be considered a primary intervention site. Further research on the role of cocaine and amphetamine in heroin-related overdose is indicated.     

Liposomes and niosomes as potential carriers for dermal delivery of minoxidil

The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes were made with two different commercial mixtures of alkylpolyglucoside (APG) surfactants (Oramix NS10, Oramix CG110), Chol and dicetylphosphate. Minoxidil skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either drug vesicular systems or propylene glycol-water-ethanol solution (control). Penetration of minoxidil in epidermal and dermal layers was greater with liposomes than with niosomal formulations and the control solution. These differences might be attributed to the smaller size and the greater potential targeting to skin and skin appendages of liposomal carriers, which enhanced globally the skin drug delivery. The greatest skin accumulation was always obtained with non-dialysed vesicular formulations. No permeation of minoxidil through the whole skin thickness was detected in the present study irrespective of the existence of hair follicles. Alcohol-free liposomal formulations would constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.     

Reductions in non-fatal overdose after drug misuse treatment: results from the National Treatment Outcome Research Study (NTORS)

Few studies have reported changes in rates of overdose after drug misuse treatment. This paper investigates changes in non-fatal overdose between treatment intake and 1 year follow-up among a sample of 753 clients recruited to the National Treatment Outcome Research Study (NTORS). A relatively high rate of overdose (15%) was reported during the 3 months prior to treatment. Variables predictive of overdose at intake to treatment included injecting, frequency of benzodiazepine and cocaine use, quantity of alcohol consumption, and levels of anxiety. At 1 year follow-up, the rate of non-fatal overdose had fallen to 6%. Reduced rates of non-fatal overdose were found for clients treated in both residential and community treatment settings. Reductions in overdose were linked to improvements in frequency of drug use and lower rates of injecting. Clients who overdosed at follow-up showed no improvements in their substance use, except for frequency of crack cocaine use. The risk of non-fatal overdose at 1 year was associated with injecting and multiple drug use. These findings support the view that treatment an important role can play in reducing deaths among drug misusers.     

Topical minoxidil. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in alopecia areata and alopecia androgenetica

When minoxidil is administered orally for periods in excess of 1 month, hypertrichosis occurs as a side effect in a majority of patients. Consequently, topical minoxidil has been developed to try to improve hair growth in patients with alopecia areata and alopecia androgenetica. Preliminary studies have shown that topical minoxidil promotes cosmetically acceptable hair regrowth in a variable proportion of patients with alopecia areata. Data from a large multicentre trial indicate that cosmetically worthwhile results are achieved in about one-third of subjects with alopecia androgenetica after 1 year of treatment. A much higher proportion (about 80%) of patients with alopecia androgenetica exhibited some non-vellus hair regrowth after 1 year, and whether more of these patients would develop a cosmetically acceptable result with a longer treatment period is an important area of future investigation. Initial indications suggest that less severe disease is a predictor of likely response. Thus, topical minoxidil would seem to be a useful treatment modality for patients with alopecia androgenetica--a disease for which no other safe and effective drug therapy exists. Results from treating patients with alopecia areata with topical minoxidil, although encouraging, have been more variable and require further evaluation. Even though a number of questions remain to be answered about topical minoxidil (as would be expected at this stage in its development), it would seem to be the first available drug with the potential to promote substantial hair regrowth in these divergent diseases.     

Accidental and deliberate overdose among opiate addicts in methadone maintenance treatment: are deliberate overdoses systematically different?

The frequency of accidental or deliberate overdose was investigated among 200 opiate addicts in methadone substitution treatment in clinics in Edinburgh and south London. One hundred and three of the participants reported a mean of 3.4 overdoses, with 71 (69%) reporting that their most recent overdose was accidental, 27 (26%) deliberate-the remainder were uncertain. Those whose last overdose was deliberate were more likely to have been prescribed diazepam at that time and were more depressed at the time of interview. Differentiation by self-reported reason for overdose suggests that treatment providers should distinguish between accidental and deliberate overdose in developing overdose prevention strategies.     

HPLC法测定米诺地尔搽剂中米诺地尔的含量

目的建立用于测定米诺地尔搽剂中米诺地尔含量的HPLE法。方法采用HPLC法测定,色谱柱：Hypersil ODS2 （250mm×4．6mm,5μm）,流动相：V（甲醇）：V（0．1％三乙胺水溶液）=25：75,检测波长285nm,柱温30℃,流速1mL·min^-1。结果米诺地尔在质量浓度6．6—39．6mg·L^-1内与峰面积之间呈现良好的线性关系（r=0．9996）,平均回收率为107．99％,RSD为0．99％。结论本方法简便、灵敏度高,能准确检测米诺地尔搽剂中米诺地尔的含量,可作为米诺地尔搽剂质量控制的有效测量方法。     

Documenting need for naloxone distribution in the Los Angeles County jail system

BackgroundThe Los Angeles County Jail system is the largest jail system in the United States, with an average daily inmate population of 17,024 in 2017. Existing literature shows the weeks following release from incarceration are associated with increased risk of overdose death among individuals who previously used opioids. One response is to train inmates in overdose prevention and response (OPR) and to provide the opioid antagonist naloxone on release. However, in large jail systems training all inmates can be logistically and financially difficult, leading to interest identifying individuals most likely to benefit from such programs.MethodIn 2017, the Los Angeles County Office of Diversion and Reentry collaborated with the Los Angeles County Sheriff Department to conduct an OPR needs assessment evaluation with all inmates entering the jail over a two week period.Results3781 inmates provided complete data for this analysis (3315 men, 466 women). 17% reported using opioids within the last 12 months, 7% reported witnessing an overdose within the last 12 months, and 5% report ever having received medication assisted treatment (MAT). 39% reported interest in being trained in overdose prevention and response. The single largest predictor of interest in OPR was being present at an overdose in the past year.ConclusionOur results suggest OPR should be provided to all inmates who opt-in to receiving training regardless of other risk factors. Our results also suggest this population has had little prior exposure to MAT and incarceration could represent a significant opportunity to provide such evidence-based treatments.     

Detoxication treatment for carbamazepine and lithium overdose

This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.