Relative Uptake of Minoxidil Into Appendages and Stratum Corneum and Permeation Through Human Skin in Vitro

Total Page:16

File Type:pdf, Size:1020Kb

Relative Uptake of Minoxidil Into Appendages and Stratum Corneum and Permeation Through Human Skin in Vitro Relative Uptake of Minoxidil into Appendages and Stratum Corneum and Permeation through Human Skin In Vitro JEFFREY E. GRICE,1 SUSAN CIOTTI,2 NORMAN WEINER,3 PETER LOCKWOOD,2 SHEREE E. CROSS,1 MICHAEL S. ROBERTS1 1Therapeutics Research Unit, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Brisbane, Woolloongabba, Qld 4102, Australia 2Formerly Pfizer Global Research and Development, Ann Arbor, Michigan 3College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109 Received 25 March 2009; revised 8 May 2009; accepted 19 May 2009 Published online 18 June 2009 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.21856 ABSTRACT: We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formula- tions containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing for- mulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formula- tion after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil. ß 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:712–718, 2010 Keywords: absorption; formulation vehicle; membrane transport; passive diffusion; skin; transdermal drug delivery INTRODUCTION there have been a number of studies examining appendageal deposition, particularly of nanopar- The differential targeting of topically applied com- ticles,1 and other work aiming to determine the pounds into appendages, stratum corneum (SC) contribution of appendageal transport to skin and through skin is an important goal. While penetration,2 to our knowledge there are no reports examining the deposition of therapeutic compounds to all three areas. The aim of this work Susan Ciotti’s present address is NanoBio Corporation, was to study uptake, through a quantitative esti- 2311 Green Road, Suite A, Ann Arbor, MI 48105. Peter Lockwood’s present address is Pfizer Global Research mate of deposition of the model therapeutic agent, and Development, Groton, CT 06340. minoxidil, into appendages, SC, and through Correspondence to: Michael S. Roberts (Telephone: þ61-7- human skin, under the influence of different 3240-5803; Fax: þ61-7-3240-5806; E-mail: [email protected]) vehicles. Journal of Pharmaceutical Sciences, Vol. 99, 712–718 (2010) There is increasing recognition of the contribu- ß 2009 Wiley-Liss, Inc. and the American Pharmacists Association tions to transdermal delivery made by ‘‘shunt 712 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 99, NO. 2, FEBUARY 2010 RELATIVE UPTAKE OF MINOXIDIL INTO APPENDAGES AND STRATUM CORNEUM 713 pathways’’ or ‘‘appendageal transport,’’1,3 parti- within the follicle. Three prototype formulations cularly at early times.4 This contribution has been with differing ethanol, PG, and water content evaluated, with varying degrees of acceptance, by were chosen; in proportion by volume of 60:20:20, indirect methods, for example, by a comparison 80:20:0 (no water) and 0:80:20 (no ethanol), between areas of different follicular density5 or respectively. Finite doses of 2% minoxidil (5 mL/ between intact and scarred skin,6 by physical cm2) were applied to excised full thickness human blocking of follicular openings,7 or by the use of skin. This dose is similar to that applied to the the in vitro skin sandwich technique.8 In addition, human scalp under ‘‘in use’’ conditions (3–5 mL/ rather than regarding follicles as shunts for trans- cm2). The results were interpreted in terms of dermal delivery, some attention has been given to solvent evaporation and individual vehicle effects. direct targeting of hair follicles by therapeutic agents, such as for acne and alopecia. To this end, attempts have been made to quantitate material retained in follicles after topical application of EXPERIMENTAL model penetrants such as dyes9 and nanoparti- cles,1 but little has been done with therapeutic Chemicals compounds and the area remains difficult and 3H-minoxidil (Minoxidil, [piperyl-3,4-3H], ART- incompletely validated.10 A useful approach is 0711-250mCi) was purchased from American that of differential stripping.11 Introduced by Radiolabeled Chemicals, Inc. (St. Louis, MO). Marks and Dawber,12 this technique allows Minoxidil was supplied by the Therapeutics quantitation of SC retention by tape stripping Research Unit. Ethanol and PG were purchased and of follicular retention by cyanoacrylate from Sigma–Aldrich Pty. Ltd. (Sydney, Australia). casting.1 The scintillation cocktail used was Emulsifier- The targeting of topically applied substances Safe (PerkinElmer Pty Ltd, Melbourne, Austra- to particular skin sites can be approached by lia). For cyanoacrylate casting, we used ‘‘Quick manipulating the components of the formulation. Fix Supa Glue’’ (Selleys Pty Ltd, Padstow, In this work, we chose to prepare formulations Australia). Formulations containing 2% (g/mL) with different proportions of three common minoxidil and a trace amount of 3H-minoxidil vehicles, ethanol, propylene glycol (PG), and (approx. 1 mCi/7 mL) were prepared in three water. Ethanol and PG rapidly diffuse into different vehicle mixtures. These contained (by the SC13 and may act as penetration enhancers volume) 60% ethanol, 20% PG, and 20% water by a variety of mechanisms.13–15 Of interest here (formulation 1); 80% ethanol and 20% PG are the effects on membrane properties to alter (formulation 2); and 80% PG and 20% water drug permeation, following alcohol diffusion into (formulation 3). In the following, these formula- the membrane. As well, ethanol could potentially tions will be designated 60:20:20, 80:20:0, and extract or solubilize sebum to promote follicular 0:80:20, respectively. delivery in some cases. The use of water in formulations aids skin hydration, thus enhancing transdermal delivery of many drugs. This may be Human Skin Membranes particularly important when vehicles which tend to desiccate the skin are present, such as ethanol Human abdominal skin was obtained from volun- and PG. teers undergoing elective surgery. The collection While the mechanism of action of the model of skin was approved by the Princess Alexandra compound, minoxidil remains unclear, the hair Hospital Research Committee (Approval no. 097/ follicle has been regarded as the site of action16 090, administered by the University of Queens- and a recent report identified K(ATP) channels land Human Ethics Committee) and donors gave responsive to minoxidil located in human follicu- informed written consent. Full thickness skin, lar dermal papillae.17 The uptake of minoxidil was which was used in the majority of experiments, studied by measuring penetration into the recep- was separated from underlying fat and epidermal tor of Franz diffusion cells and by differential and dermal membranes were prepared from full stripping, consisting of tape stripping (20 times) to thickness skin by floating the skin in water at sample SC content, which reflects partitioning of 608C for 1 min and peeling off the epidermal layer. minoxidil into the skin barrier layer and cyanoa- Both full thickness skin and epidermal mem- crylate casting to sample minoxidil deposited branes were stored frozen at À208C until use. DOI 10.1002/jps JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 99, NO. 2, FEBUARY 2010 714 GRICE ET AL. In Vitro Permeation Studies adhesive tape to the exposed skin surface and careful removal, up to a maximum of 20 times. The experiments were performed using full Individual tapes were placed into separate scin- thickness skin as described above, from three tillation vials and soaked overnight with 2 mL different donors (five replicates per skin) in glass scintillation fluid (Emulsifier-Safe) before vortex- horizontal static Franz-type diffusion cells, using ing and quantitation by liquid scintillation phosphate buffered saline, pH 7.4 (PBS) as the counting (LSC). The total amount of minoxidil receptor phase. The exposed skin surface area was deposited within the SC was obtained by summa- 1.33 cm2 in all cases. The diffusion cells were tion of the amounts measured on the individual placed in a water bath, to maintain the receptor tapes. Results for the first two tapes were not phase temperature at 358C, over a magnetic included, as this represents unabsorbed surface 15 point stirring plate. Magnetic stirrer bars in material only. the bottom of each receptor chamber maintained Following tape stripping, follicular casts were mixing of the receptor fluid. The prepared Franz prepared. One drop of superglue was placed on a cells remained in the water bath for a minimum of glass microscope slide, which was then pressed 30 min before dosing, to ensure the skin was onto the surface of the stripped skin and held in adequately hydrated. After hydration, resistance
Recommended publications
  • Topically Applied Minoxidil in Baldness
    Review Topically Applied Minoxidil in Baldness ERVIN NOVAK,M.D., THOMASJ. FRANZ, M.D., JOHN T. HEADINGTON,M.D., AND RONALD C. WESTER,PH.D. From the Upjohn Company, Kalamazoo, Michigan, School idil and its metabolites can be removed by hemodi- of Medicine, University of Washington, Seattle, alysis. Washington, Medical School, University of Michigan, Ann Fluid retention and hypertrichosis are the most Arbor, Michigan, and School of Medicine and School of Pharmacy, University of California, San Francisco, California commonly occurring side effects of minoxidil. Hair regrowth in a patient with male pattern baldness was described in a case report of a hypertensive patient treated twice daily with 20 mg oral minoxidil.6 The Minoxidil, an orally administered, peripheral va- extensive hair regrowth continued after 10 months sodilator used to treat hypertension, causes hypertri- of therapy. New and increased hair growth as a side chosis in more than 80% of users. The drug reduces effect was also detected in an early clinical study elevated blood pressure by decreasing peripheral involving five of eight patients on oral minoxidil vascular resistance. Chemically, minoxidil is 2,4-di- therapy for 2 month^.^ Zappacosta' reported reversal amino-6-piperidinopyrimidine-3-oxide; it is soluble in of baldness in a patient on minoxidil for the treatment water to the extent of approximately 2 mg/ml, is of hypertension. more readily soluble in propylene glycol or ethanol, After the third week of therapy with oral minoxidil, and is nearly insoluble in acetone, chloroform, or hypertrichosis usually appears between the eyebrows ethyl acetate. Following oral administration of minox- and the hair line, in the malar and temporal areas, idil and in association with the reduction in peripheral on the backs of the arms, on the shoulders, and on vascular resistance, cardiac output is augmented, salt the legs.
    [Show full text]
  • Label-Free Cell Phenotypic Profiling Decodes the Composition And
    OPEN Label-free cell phenotypic profiling SUBJECT AREAS: decodes the composition and signaling POTASSIUM CHANNELS SENSORS AND PROBES of an endogenous ATP-sensitive Received potassium channel 28 January 2014 Haiyan Sun1*, Ying Wei1, Huayun Deng1, Qiaojie Xiong2{, Min Li2, Joydeep Lahiri1 & Ye Fang1 Accepted 24 April 2014 1Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, NY 14831, United States of Published America, 2The Solomon H. Snyder Department of Neuroscience and High Throughput Biology Center, Johns Hopkins University 12 May 2014 School of Medicine, Baltimore, Maryland 21205, United States of America. Current technologies for studying ion channels are fundamentally limited because of their inability to Correspondence and functionally link ion channel activity to cellular pathways. Herein, we report the use of label-free cell requests for materials phenotypic profiling to decode the composition and signaling of an endogenous ATP-sensitive potassium should be addressed to ion channel (KATP) in HepG2C3A, a hepatocellular carcinoma cell line. Label-free cell phenotypic agonist Y.F. (fangy2@corning. profiling showed that pinacidil triggered characteristically similar dynamic mass redistribution (DMR) com) signals in A431, A549, HT29 and HepG2C3A, but not in HepG2 cells. Reverse transcriptase PCR, RNAi knockdown, and KATP blocker profiling showed that the pinacidil DMR is due to the activation of SUR2/ Kir6.2 KATP channels in HepG2C3A cells. Kinase inhibition and RNAi knockdown showed that the pinacidil * Current address: activated KATP channels trigger signaling through Rho kinase and Janus kinase-3, and cause actin remodeling. The results are the first demonstration of a label-free methodology to characterize the Biodesign Institute, composition and signaling of an endogenous ATP-sensitive potassium ion channel.
    [Show full text]
  • Acquired Hypertrichosis of the Periorbital Area and Malar Cheek
    PHOTO CHALLENGE Acquired Hypertrichosis of the Periorbital Area and Malar Cheek Caitlin G. Purvis, BS; Justin P. Bandino, MD; Dirk M. Elston, MD An otherwise healthy woman in her late 50s with Fitzpatrick skin type II presented to the derma- tology department for a scheduled cosmetic botulinum toxin injection. Her medical history was notable only for periodic nonsurgical cosmetic procedures including botulinum toxin and dermal fillers, and she was not taking any daily systemic medications. Duringcopy the preoperative assess- ment, subtle bilateral and symmetric hypertricho- sis with darker terminal hair formation was noted on the periorbital skin and zygomatic cheek. Uponnot inquiry, the patient admitted to purchas- ing a “special eye drop” from Mexico and using it regularly. After instillation of 2 to 3 drops per eye, she would laterally wipe the resulting excess Dodrops away from the eyes with her hands and then wash her hands. She denied a change in eye color from their natural brown but did report using blue color contact lenses. She denied an increase in hair growth elsewhere including the upper lip, chin, upper chest, forearms, and hands. She denied deepening of her voice, CUTIS acne, or hair thinning. WHAT’S THE DIAGNOSIS? a. acetazolamide-induced hypertrichosis b. betamethasone-induced hypertrichosis c. bimatoprost-induced hypertrichosis d. cyclosporine-induced hypertrichosis e. timolol-induced hypertrichosis PLEASE TURN TO PAGE E21 FOR THE DIAGNOSIS From the Department of Dermatology, Medical University of South Carolina, Charleston. The authors report no conflict of interest. Correspondence: Justin P. Bandino, MD, 171 Ashley Ave, MSC 908, Charleston, SC 29425 ([email protected]).
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Ambetter 90-Day-Maintenance Drug List- 2020
    Ambetter 90-Day-Maintenance Drug List Guide to this list: What is Ambetter 90‐Day‐Maintenance Drug List? Ambetter 90‐Day‐Supply Maintenance Drug List is a list of maintenance medications that are available for 90 day supply through mail order or through our Extended Day Supply Network. How do I find a pharmacy that is participating in Extended Day Supply Network? To find a retail pharmacy that is participating in our Extended Day Supply Network please consult information available under Pharmacy Resources tab on our webpage. Alternatively, you can utilize our mail order pharmacy. Information on mail order pharmacy is available in Pharmacy Resources tab on our webpage. Are all formulary drugs covered for 90 day supply? No, certain specialty and non‐specialty drugs are excluded from 90 day supply. Please consult 90‐Day‐ Supply Maintenance Drug List for information if your drug is included. A Amitriptyline HCl Acamprosate Calcium Amlodipine Besylate Acarbose Amlodipine Besylate-Atorvastatin Calcium Acebutolol HCl Amlodipine Besylate-Benazepril HCl Acetazolamide Amlodipine Besylate-Olmesartan Medoxomil Albuterol Sulfate Amlodipine Besylate-Valsartan Alendronate Sodium Amlodipine-Valsartan-Hydrochlorothiazide Alendronate Sodium-Cholecalciferol Amoxapine Alfuzosin HCl Amphetamine-Dextroamphetamine Aliskiren Fumarate Anagrelide HCl Allopurinol Anastrozole Alogliptin Benzoate Apixaban Alosetron HCl Arformoterol Tartrate Amantadine HCl Aripiprazole Amiloride & Hydrochlorothiazide Armodafinil Amiloride HCl Asenapine Maleate Amiodarone HCl Aspirin-Dipyridamole
    [Show full text]
  • Study Protocol 7
    Title: Role of Neurogenic Inflammation and Topical 6% Gabapentin Therapy in Symptomatic Scarring Alopecia Protocol Number: 1308M40801 Study Drug: Gabapentin 6% Solution Principal Investigator: Maria Hordinsky, MD 612-625-8625 Study Team: Rehana Ahmed-Saucedo, MD, PhD Margareth Pierre-Louis, MD Elisabeth Hurliman, MD, PhD Trial Site: University of Minnesota, Department of Dermatology MMC 98 Minneapolis, MN 55455 Laboratory: University of Minnesota, Fairview Laboratory 516 Delaware St. Minneapolis, MN 55455 Masonic Clinical Research Unit MMC 405, 420 Delaware St. Minneapolis, MN 55455 Version Date: January 12, 2016 CONFIDENTIAL This is a University of Minnesota clinical research trial document that contains confidential information. It is intended solely for the recipient clinical investigator(s) and must not be disclosed to any other party. The material may be used only for evaluating or conducting clinical investigations; any other proposed use requires written consent from the University of Minnesota Department of Dermatology. Scarring Alopecia-Gabapentin Study Version 5 | Approved 01.28.2016 Page ii Table of Contents STUDY SUMMARY ................................................................................................................................. 1 1 INTRODUCTION ............................................................................................................................... 2 1.1 BACKGROUND .............................................................................................................................
    [Show full text]
  • Valproate-Induced Hair Loss: What to Tell Patients
    P earls Valproate-induced hair loss: What to tell patients Shailesh Jain, MD, MPH, ABDA, and Beth Beste, MS Teach patients s. B, age 29, has bipolar disorder may lead to low serum and liver tissue bio- that certain that is stabilized by valproate, 1,250 tinidase enzyme4; a major clinical manifes- supplements and Mmg/d. After 1 month of treatment, tation of biotin deficiency is alopecia. she shows scalp hair loss. She takes no other lifestyle changes medications and is distressed because she had 2 Tell patients to avoid taking valproate may reduce this never experienced such copious hair loss. Ms. during meals to prevent its chelating effect on usually temporary B’s blood valproate level is at a therapeutic food. The chelating effect of valproate makes side effect level. She wants to know if the hair loss will metals that facilitate hair growth, such as zinc be permanent and what she can do to stop it. and selenium, unavailable for absorption.5 Up to 28% of patients who take valproate suffer temporary alopecia.1,2 In most cases, 3 Recommend zinc and selenium supple- hair loss is associated with long-term valpro- ments, which can help stop further hair loss ate pharmacotherapy. Hair loss appears to and regenerate hair.5 be dose-related2 and may be more common in women than in men. Usually patients will 4 Suggest practical advice for hair care, in- report gradual but steady hair loss, com- cluding using soft brushes and mild sham- monly beginning 2 to 6 months after initiat- poos and avoiding dyes, heated curlers, and ing treatment.3 Complete hair loss is rare and hair dryers.
    [Show full text]
  • IEHP Dualchoice Cal Mediconnect Formulary Maintenance Drug List
    IEHP DualChoice Cal MediConnect (Medicare-Medicaid Plan) Formulary Maintenance Drug List The following formulary medications may be approvable up to a three-month supply. Certain medications on this list may require prior approval from the plan based on existing criteria before being covered. For coverage information please see our formulary located on our website. BRAND GENERIC STREGTH DOSAGE FORM ABACAVIR ABACAVIR SULFATE 300 MG TABLET ABACAVIR ABACAVIR SULFATE 20 MG/ML SOLUTION TRIUMEQ ABACAVIR SULFATE/DOLUTEGRAVIR 600-50-300 TABLET SODIUM/LAMIVUDINE ABACAVIR-LAMIVUDINE ABACAVIR SULFATE/LAMIVUDINE 600-300MG TABLET ABACAVIR-LAMIVUDINE- ABACAVIR SULFATE/LAMIVUDINE/ZIDOVUDINE 150-300 MG TABLET ZIDOVUDINE TYMLOS ABALOPARATIDE 80MCG/DOSE PEN INJCTR ORENCIA ABATACEPT 125 MG/ML SYRINGE ORENCIA CLICKJECT ABATACEPT 125 MG/ML AUTO INJCT ORENCIA ABATACEPT 50MG/0.4ML SYRINGE ORENCIA ABATACEPT 87.5MG/0.7 SYRINGE VERZENIO ABEMACICLIB 50 MG TABLET VERZENIO ABEMACICLIB 100 MG TABLET VERZENIO ABEMACICLIB 150 MG TABLET VERZENIO ABEMACICLIB 200 MG TABLET ABIRATERONE ACETATE ABIRATERONE ACETATE 500 MG TABLET ABIRATERONE ACETATE ABIRATERONE ACETATE 250 MG TABLET YONSA ABIRATERONE ACETATE, SUBMICRONIZED 125 MG TABLET CALQUENCE ACALABRUTINIB 100 MG CAPSULE ACAMPROSATE CALCIUM ACAMPROSATE CALCIUM 333 MG TABLET DR ACARBOSE ACARBOSE 25 MG TABLET ACARBOSE ACARBOSE 50 MG TABLET ACARBOSE ACARBOSE 100 MG TABLET ACEBUTOLOL HCL ACEBUTOLOL HCL 200 MG CAPSULE ACEBUTOLOL HCL ACEBUTOLOL HCL 400 MG CAPSULE ACETAZOLAMIDE ER ACETAZOLAMIDE 500 MG CAPSULE ER ACETAZOLAMIDE
    [Show full text]
  • Dialyzability of Medications During Intermittent Hemodialysis
    DialyzeIHD: Dialyzability of Medications During Intermittent Hemodialysis % Dialyzed % Dialyzed % Dialyzed % Dialyzed IHD Dosing; Administration IHD Dosing; Administration IHD Dosing; Administration IHD Dosing; Administration Timing Drug (Type of Drug (Type of Drug (Type of Drug (Type of Timing Around HD Session Timing Around HD Session Around HD Session Dialyzer) Timing Around HD Session Dialyzer) Dialyzer) Dialyzer) 0.25-0.5mg PO Q8H PRN, Insulin Aspart, Pentamidine 0 4mg/kg IV Q24-36H, Not recommended for use, Clonazepam N/A Reduce to 25-50% of normal dose Acarbose N/A Administer anytime during HD Insulin Detemir, Isethionate (N/A) Administer anytime during HD Administer anytime during HD N/A and titrate, Administer anytime Insulin Glargine, 0.1-0.4mg PO Q8-12H, during HD Normal dose and titrate based on 100-150mg PO Q12-24H, <5 Insulin Lispro Acebutolol N/A Clonidine Administer anytime during HD; No target free or corrected total Administer post-HD (Low Flux) Phenytoin Dose post-HD if hypotensive 75-300mg PO Q24H, (Low Flux) phenytoin level, Normal dose based on indication, 0 Administer anytime during HD Acetaminophen N/A 75mg PO Q24H, Irbesartan Administer anytime during HD; Dose Administer anytime during HD Clopidogrel N/A (N/A) Administer anytime during HD post-HD if hypotensive No 15-45mg PO Q24H, Pioglitazone 2.5-5mg/kg IV/PO Q24H, (N/A) Administer anytime during HD 40-60 250-500mg PO Q6H or 1-2g IV Q4- 100mg IV weekly to monthly, Acyclovir Administer post-HD over 60 Cloxacillin N/A Iron Dextran N/A (N/A) 6H, Administer anytime
    [Show full text]
  • Formulation of Sodium Valproate Nanospanlastics As a Promising Approach for Drug Repurposing in the Treatment of Androgenic Alopecia
    pharmaceutics Article Formulation of Sodium Valproate Nanospanlastics as a Promising Approach for Drug Repurposing in the Treatment of Androgenic Alopecia Farid. A. Badria 1,* , Hassan A. Fayed 2, Amira K. Ibraheem 3, Ahmed F. State 2 and Eman A. Mazyed 4 1 Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 33516, Egypt 2 Department of Dermatology, Faculty of Medicine, Mansoura University, Mansoura 33516, Egypt; [email protected] (H.A.F.); [email protected] (A.F.S.) 3 Mansoura Dermatology and Leprosy Hospital, Mansoura 35511, Egypt; [email protected] 4 Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; [email protected] * Correspondence: [email protected]; Tel.: +20-100-1762927 Received: 12 August 2020; Accepted: 9 September 2020; Published: 11 September 2020 Abstract: Sodium valproate (SV) is an antiepileptic drug that is widely used in the treatment of different seizure disorders. The topical SV has a hair regenerative potential through activating the Wnt/β-catenin pathway and anagen phase induction. The aim of the current investigation was to fabricate nanospanlastics of SV for improving its dermal delivery by providing prolonged drug effect and increasing its permeability for treatment of androgenic alopecia (AGA). SV-loaded nanospanlastics were formulated according to 23 factorial design by ethanol injection method using a non-ionic surfactant (Span 60) and edge activators (EAs), such as Tween 80 and Cremophor RH 40, to explore the influence of different independent variables on entrapment efficiency (EE%) and percentage drug released after 12 h (Q12h) in order to choose the optimized formula using Design-Expert software.
    [Show full text]
  • HEB Minoxidil Topical Solution USP, 5% Drug Facts
    MINOXIDIL FOR MEN- minoxidil solution H E B ---------- HEB Minoxidil Topical Solution USP, 5% Drug Facts Active ingredient Minoxidil 5% w/v Purpose Hair regrowth treatment for men Use to regrow hair on the top of the scalp (vertex only, see pictures on side of carton) Warnings For external use only. For use by men only. Flammable: Keep away from fire or flame Do not use if • you are a woman • your amount of hair loss is different than that shown on the side of this carton or your hair loss is on the front of the scalp. Minoxidil topical solution 5% is not intended for frontal baldness or receding hairline. • you have no family history of hair loss • your hair loss is sudden and/or patchy • you do not know the reason for your hair loss • you are under 18 years of age. Do not use on babies and children. • your scalp is red, inflamed, infected, irritated, or painful • you use other medicines on the scalp Ask a doctor before use if you have heart disease When using this product • do not apply on other parts of the body • avoid contact with the eyes. In case of accidental contact, rinse eyes with large amounts of cool tap water. • some people have experienced changes in hair color and/or texture • it takes time to regrow hair. Results may occur at 2 months with twice a day usage. For some men, you may need to use this product for at least 4 months before you see results. • the amount of hair regrowth is different for each person.
    [Show full text]
  • Sodium Valproate Induced Alopecia: a Case Series
    DOI: 10.7860/JCDR/2017/28564.10658 Case Series Sodium Valproate Induced Alopecia: A Section Case Series Pharmacology SEREEN ROSE THOMSON1, VINAY MAMULPET2, SHALINI ADIGA3 ABSTRACT Drug induced alopecia may range from a barely detectable shedding to an irreversible baldness. Alopecia associated with valproate is a dose-dependent and reversible side effect. We hereby report, three cases of alopecia that occurred in patients who received sodium valproate for various neurological conditions. In all three cases, long term exposure of valproate therapy led to the development of alopecia which eventually resolved after dose reduction or discontinuation. The Naranjo’s causality assessment scale indicated valproate as the probable cause of the alopecia in all our patients. Keywords: Adverse drug reaction, Anticonvulsant, Hair loss, Naranjo’s scale CASE SERIES scalp examination there was non-scarring and bitemporal recession Sodium valproate was originally developed as an anti-epileptic and of hair. His 1st episode of GTCS was at the age of 15 years, when he nd later approved for its use in bipolar disorders, migraine prophylaxis was started on tablet phenytoin 500 mg twice a day. A 2 episode and off labelly in the treatment of alcohol dependence, bipolar of GTCS occurred the next year, when phenytoin was changed depression and aggression. Therefore, it is important to keep a to valproate 500 mg. Metabolic and other laboratory parameters watch at the common and uncommon Adverse Drug Reactions [{Fasting blood sugar–99 mg/dl (70-100 mg/dl), Total cholesterol- (ADR) occurring with this drug. Diffuse and non-scarring alopecia is 180 mg/dl (140-200 mg/dl), Triglycerides-142 mg/dl (60-150 mg/ one of the uncommon ADR associated with valproate and has to be dl), HDL-37 (40-65 mg/dl), LDL-114.6 mg/dl (50-130 mg/dl), looked into and treated with utmost caution.
    [Show full text]