Minoxidil solution

In the pharmaceutical synthesis industry, piperidine is used in some drugs such as budipine (antiparkinsonian drug), raloxifene (used in the prevention of osteoporosis), minoxidil (an oral drug to treat high blood pressure). Minoxidil has the interesting side effect of hair growth and reverses hair loss. A two percent minoxidil solution can be used to treat this condition. 

In an open comparative study of androgenetic alopecia in 90 men oral finasteride (1 mg/day for 12 months n = 65) was compared with 5% topical minoxidil solution twice daily (n = 25) (22). The cure rates were 80% for oral finasteride and 52% for topical minoxidil. The adverse effects were all mild, and did not lead to withdrawal of treatment. Of the 65 men given oral finasteride, six had loss of libido, and one had an increase in body hair at other sites irritation of the scalp was seen in one of those who used minoxidil. These adverse events disappeared as soon as the treatment was withdrawn. The laboratory data did not show any statistically or clinically significant changes from baseline values to the endpoint, except for the serum total testosterone concentration, which was increased, and free testosterone and serum prostate-specific antigen in the finasteride group which were reduced from baseline values. 

Sodium benzoate was shown by Asker and Harris (108) to be an effective photostabilizer for physostigmine sulfate solutions. The photostability of minoxidil solution is also enhanced by sodium benzoate (48). Figure 17 shows the absorption curves of sodium benzoate and minoxidil. As can be seen in the figure, sodium benzoate absorbs radiation in the same range as minoxidil, thus acting as a photoprotective agent for the drug (109). 

The photostability of minoxidil solution in the presence of various photostabilizers under fluorescent radiation from cool white fluorescent tubes is presented in Table 9. 

Chinnian D, Asker AF. Photostability profiles of minoxidil solutions PDA. J Pharm Sci... 

Chinnian DM. Photostability of Minoxidil Solutions. Master Thesis, Florida A M University, Tallahassee, FL, 1995. 

A fetus had an extremely hypotrophic candal body pole, aplasia of the lower spine, and complete renal agenesis diagnosed in the second trimester by ultrasound. The mother had used minoxidil solution to prevent hair loss for 4 years before and during gestation. She had also taken co-trimoxazole during the first trimester. She was not diabetic and had no history of familial genetic disorders. 

Despite the poor transdermal absorption of minoxidil, in 7 out of 30 non-hypertensive patients treated with 3% minoxidil solution twice daily, there was a significant fall in blood pressure (16). 

Some patients using minoxidil solution had increased hair growth outside the area of drug application (SEDA-18, 175), which suggests a systemic effect (17). 

A 26-year-old woman took 60 ml of minoxidil solution 5% and 1 hour later developed hypotension (75/ 40 mmHg) and tachycardia (130/minute). She was... 

Friedman ES, Friedman PM, Cohen DE, Washenik K. Allergic contact dermatitis to topical minoxidil solution etiology and treatment. J Am Acad Dermatol 2002 46(2) 309-12. 

C. Minoxidil. Two adults developed profound hypotension (with tachycardia) requiring pressor support following 1.3-g and 3-g ingestions from topical minoxidil solutions. 

Over the years it has been interesting to note that many compounded products eventually become commercially available products. Recent examples might include fentanyl lozenges, minoxidil topical solution, nystatin lozenges, clindamycin topical solution, tetracaine-adrenalin-cocaine (TAG) solution, dihydroergotamine mesylate nasal spray, buprenorphine nasal spray, buffered hypertonic saline solution, and erythromycin topical solution as well as numerous other dermatological and pediatric oral liquids and some... 

Hair growth stimulants Minoxidil, 2%, 5% solution, apply 1 mL to affected areas of scalp twice daily. Rogaine for Men, Rogaine for Women, Rogaine Extra Strength for Men Minoxidil appears to directly stimulate hair follicles resulting in increased hair thickness and reduced hair loss. Treatment for four... 

Until recently, the only pharmacologic preparation approved for the treatment of AGA was minoxidil, which is applied topically as a solution... 

Drugs whose decomposition rates are influenced by the pH include doxorubicin hydrochloride (47), minoxidil (48), menadione sodium bisulfite (67), metronidazole (68), riboflavin (69), colchicine (70), tetracycline hydrochloride (71), phenobarbital (72), dacarbazine (73), furosemide (74), daunorubicin hydrochloride (75), and demeclo-cycline hydrochloride (76). Figures 3 to 6 illustrate how the pH of the solution can influence the degradation rate of some of the reported photolabile drugs. 

Figure 9 Log Kof the photodegradation of minoxidil in pH 8 phosphate buffer versus ionic strength of the solution. Source From Ref. 48.

Ferdous and Asker (76) found that demeclocycline hydrochloride solution degraded more in clear than in amber glass vials when exposed to fluorescent radiation from cool white fluorescent tubes. Amber glass was also found to provide better protection for solutions of doxorubicin hydrochloride (47), minoxidil (48), and furosemide (74). Figures 15 and 16 illustrate the effect of type of glass on photodegradation of furosemide and democlocycline hydrochloride, respectively. 

Sodium metabisulfite has been used to photostabilize solutions of minoxidil (48) and promethazine hydrochloride (120). Sodium metabisulfite, however, was found to decrease the photostability of chloramphenicol solution (86). 

Sodium thiosulfate provides a photostabilizing effect for solutions of minoxidil (48), riboflavin (69), tetracycline hydrochloride (71), and phenobarbital (72). 

It is interesting to note here that chlorominoxidil, which is present as an impurity in minoxidil, undergoes photodechlorination in solution. The Cl produced enhances the oxidation of minoxidil. Sodium thiosulfate, which is also known for its "antichlor" activity (removes chlorine, the oxidizer), helps stabilize minoxidil according to the following equation (109) ... 

Thiourea and dl-methionine are effective photoprotective agents for solutions of riboflavin (69), tetracycline hydrochloride (71), doxorubicin hydrochloride (77), reserpine (106), and potassium iodide (121). Thiourea enhances the photostability of solutions of minoxidil (48) and furosemide solution (74). Dl-methionine increases the photostability of ascorbic acid solutions (122). 

Minoxidil is a vasodilator selective for arterioles rather than for veins, similar to diazoxide and hydralazine. Like the former, it acts through its sulphate metabolite as an ATP-dependent potassium channel opener. It is highly effective in severe hypertension, but causes increased cardiac output, tachycardia, fluid retention and hypertrichosis. The hair growth is generalised and although a cosmetic problem in women, it has been exploited as a topical solution for the treatment of baldness in men. 

Topical minoxidil stimulates new hair growth and arrests loss of hair in androgenic alopecia. Minoxidil is poorly absorbed through the skin (less than 4%) (1), and plasma concentrations of minoxidil are far less than 10% of the mean minoxidil concentration present 2 hours after oral ingestion of 5 mg, the lowest dose for the treatment of hypertension (2). Its adverse effects after topical apph-cation are therefore usually limited to the apphcation site on the scalp. They include irritant contact dermatitis, allergic contact dermatitis, and exacerbation of seborrheic dermatitis. These effects are seen in 5.7% of patients who use a 5% solution and in 1.9% of those who use a 2% formulation (3). 

In some countries, an extra-strength solution of minoxidil is available over the counter for hair regrowth treatment in men. Ingestion of a large dose in a suicide attempt has been reported (21). 

Minoxidil topical. solution is u.scd to treat alopecia andro-genitica (male pattern baldness). Although (he mechanism is not clearly undcrsItKxl. topical minoxidil is believed to increa.se cutaneous bhxid How. which may stimulate hair growth. The stimulation of hair growth is attributed to va.so-dilation in the vicinity of application of the drug, re.sulting in better nourishment of (he local hair follicle.s. 

Minoxidil (1) Rogaine Upjohn Androgenetic alopecia (men and women)" 2%,5% solutions Topical application twice daily OTC... 

Adverse Effects. The side effects of topical minoxidil are mainly local, caused by skin irritation and contact dermatitis. Systemic side effects are uncommon because of limited percutaneous absorption, but diffuse hypertrichosis of the face and limbs has been reported with the 5% solution and was attributed to systemic absorption of the drug (84). Although topical minoxidil does not change blood pressure in healthy subjects, it increases heart rate by 3-5 beats/min and slightly increases the left ventricular end-diastolic volume, cardiac output, and left ventricular mass (85). These effects are not considered clinically significant, and the potential for cardiovascular side effects is very low. 

Photochemical degradation of minoxidil in solution is likely sensitized by the impurity chlorominoxidil from the drug synthesis. An increase in the drug concentration is followed by an increased concentration of the photosensitizer, leading to a rise in the photochemical degradation rate (Chinnian and Asker, 1996). 

Parenteral formulations often contain excipients considered to be chemically stable and inert however, all excipients in a formulation may influence the photochemical stability of the product. Dextrose and sodium chloride are used to adjust tonicity in the majority of parenteral formulations. Sodium chloride can affect photochemical processes by influencing solvation of the photoreactive molecules (see Section 14.2.3). The ionic strength is reported to affect the photochemical decomposition rate of minoxidil until a saturation level is reached (Chinnian and Asker, 1996). The photostability of L-ascorbic acid (vitamin C) in aqueous solution is enhanced in the presence of dextrose, probably caused by the scavenging effect of the excipient on hydroxyl radicals mediated by the photolysis of ascorbic acid sucrose, sorbitol, and mannitol have the same effect (Ho et al., 1994). Monosaccharides (dextrose, glucose, maltose, and lactose), disaccharides (sucrose and trehalose), and polyhydric alcohols (inositol, mannitol, and sorbitol) are examples of commonly used lyo-additives in parenterals. These excipients may also affect photochemical stability of the products after reconstitution. 

Minoxidil (2% 1 mL of solution b.i.d.) is used in the treatment of male pattern baldness (alopecia androgenetica). 

Minoxidil (10 to 40 mg/day) is indicated for severe hypertension that is symptomatic or associated with target organ damage and is not manageable with maximum therapeutic doses of a diuretic plus two other antihypertensives. Topical minoxidil (Rogaine) in 0.3 to 4.5% solution is used to stimulate vertex hair growth in individuals with alopecia... 

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