A Medication Daivonex - Essay Example

Formulation Report: Daivonex Indications Daivonex is a medication for the topical treatment of chronic stable plaque type psoriasis vulgaris. The active ingredient of Daivonex is calcipotriol. It is indicated for both adults and children. For adults, the Calcipotriol cream should be applied on the affected area only twice daily, preferably in the morning and in the evening. After the initial treatment, the frequency of applications is usually reduced. After the condition has satisfactorily improved, the treatment can be discontinued. However, in instances when recurrence of psoriasis occurs, treatment with the cream may be taken up again. Daivonex is not recommended for children under 6 years of age. Children 6-12 years of age cannot be given more than 50g a week of the medication, and for children over 12 years of age, no more than 75g a week of the medication may be given to them. This medicine should also not be used in patients who have allergy to calcipotriol or to any other components of the medication. Patients with disorders of calcium metabolism should not use this product. Those with severe widespread psoriasis cannot be given this medication. Patients with high blood calcium levels or who are taking calcium and/or Vitamin D supplements cannot take this medication. For breastfeeding women, this medication should not be applied on their breasts. Proper consultation with the doctor should be done before this medication is to be prescribed and used on children (Medsafe Consumer Information, 2004). Rationale for dose form selection In adults, not more than 100 grams of cream or ointment should be used in a week and not more than 60ml of scalp solution can be used in a week. In cases where there is a need to use combination of the preparations for psoriasis, not more than 60ml of the solution plus one 30 gram of the ointment or cream tubes may be used in a week or the limit is 30 ml of the solution and two 30g tubes of Daivonex. The medicine must be applied on the psoriasis plaques forming visible coating over the affected area. Accidental application of the medicine on normal skin must be washed with water because it can cause irritation on unaffected area. It must not be applied on skin folds, on the face, and on the genitalia (Medsafe Consumer Information, 2004). The recommended dosages are set in place because more than 100g weekly of Daivonex can cause elevated serum calcium. The use of scalp and cream solutions in children has yet to be fully established; hence ointment is the preferred formulation of the medication in children. Daivonex is also not recommended for facial use because it can cause facial skin irritation. Daivonex use in pregnant women has not also been fully established, hence it is also not recommended yet for use by pregnant women (MIMS, 2009). Novel Characteristics of the formulation Daivonex is prepared as an ointment, cream, and as a scalp solution. The ointment contains the active ingredient calcipotriol (50 micrograms/g). It also contains the following ingredients: dl-alpha-tocopherol, disodium edentate, sodium phosphate-dibasic dihydrate, purified water, liquid paraffin, steareth-2, propylene glycol, and soft white paraffin. The Daivonex cream contains calcipotriol (0 micrograms/g) plus the following ingredients: disodium edentate, quaternium-15, sodium phosphate-dibasic dehydrate, cetomacrogol 1000, glycerol, liquid paraffin, cetostearyl alcohol, soft white paraffin, and purified water. The Daivonex scalp solution contains calcipotriol (50 microgram/mL) and the following ingredients: menthol, hydroxypropylcellulose, sodium citrate, propylene glycol, isopropyl alcohol, and purified water (EMedical, 2002). Main Components in the Formulation First and foremost calcipotriol is a synthetic Vitamid D3 analogue. The exact mechanism of action of this ingredient is not exactly known, however, “it is known to slow the excessive turnover of epidermal cells, by influencing keratinocyte differentiation” (Psoriasis-Guide, 2007). DL-alpha tocopherol is added in as an ingredient to act as a fat antioxidant. This ingredient is seen in other cosmetic products (ointments, creams, emulsions) which contain fat (Bienvenido a Basf en Chile, 2005). In cosmetic products disodium edentate functions as a chelating compound, preventing “ingredients from binding to any trace elements that may be present (Bye, 2009). When mineral trace elements would bind with other ingredients, the product’s texture, consistency and sometimes even smell would change. Liquid paraffin functions to reduce the erythema or redness in psoriasis (Larsen, 2008). Cetamacrogol 1000 acts as a solubilizer and emulsifying agent in Daivonex (Medical Dictionary Online, 2009). It is a non-ionic surfactant of the polyethylene glycol family. White soft paraffin functions to keep a layer of oil over the skin and prevent water from evaporating from the surface of the skin, thereby, keeping it hydrated and to prevent it from drying and cracking (Marshall, 2009). Propylene glycol also acts as a moisturizing agent for the solution. It is also a preservative and a solvent (Encyclopedia Britannica, 2009). Hydroxypropylcellulose is a water-soluble cellulose ether which has lubricating properties, again assisting in the moisturizing effects of Daivonex. Preformulation Calcipotriol appears white and white crystalline. It is freely soluble in ethanol, chloroform, and propylene glycol, but insoluble in liquid paraffin. Its solubility in water is 0.6 ug/mL, and its melting point is at 166-168oC. Calcipotriol, as a Vitamin D derivative, retains most of the properties of Vitamin D, and it has a reversible temperature-dependent equilibrium between calcipotriol and pre-calcipotriol (MedSafe, 2007). Rheological Properties In a study comparing the rheological characteristics of three Vitamin D ointments (tacalcitol, calcipotriol and calcitriol), it was revealed that viscoelastic parameters were four times higher for tacalcitol than calcipotriol and calcitriol. Fluidity was better demonstrated by calcitriol as compared to tacalcitol and calcipotriol. “The sensation of stickiness, was significantly different between tacalcitol and calcitriol, was not different between calcipotriol and calcitriol” (Marty, et.al., 2005). These results indicate that there is a relationship between rheological in vitro and sensorial in vivo results and that there may be differences in non-adherence and treatment failure based on these differences. Bioavailability Approximately, 2- 10% of the ointment from the applied dose is systemically absorbed. There is not much research on the bioavailability of cream and solution. Approximately 6% of the topically applied 0.005% ointment is absorbed through psoriatic plagues. These results in transient elevation of calcium in less than 1% of subjects treated in clinical trials (Katsung, 2004). Works Cited Bye, S. (2009) Disodium EDTA (Disodium Edetate), CremeDevie, viewed 22 March 2009 from http://www.cremedevie.com/disodium_edta.htm Calcipotriol is a useful drug for treating mild to moderate psoriasis (8 April 2000) British Medical Journal, viewed 22 March 2009 from http://www.bmj.com/cgi/content/full/320/7240/0/b Cetomacrogol 1000 (2009) Medical Dictionary Online, viewed 22 March 2009 from http://www.online-medical-dictionary.org/Cetomacrogol+1000.asp?q=Cetomacrogol+1000 Daivobet 50/500 OINTMENT (April 2007) Medsafe, viewed 22 March 2009 from http://www.medsafe.govt.nz/profs/Datasheet/d/Daivobetoint.htm Daivonex (2009), MIMS, viewed 22 March 2009 from http://www.mims.com/Page.aspx?menuid=mng&name=Daivonex+scalp+soln&brief=false Daivonex(R) ointment, cream and scalp solution (April 2002) EMedical, viewed 22 March 2009 from http://www.emedical.com.au/default.asp?pageID=56&itemID=10718&purchaseTypeID=2 Dl-alpha Tocopherol (May 2005) Bienvenido a Basf en Chile, viewed 22 March 2009 from http://www.basf.cl/carechemicals/nutricionhumana/fichastecnicas/vitaminas/liposolubles/dl_alpha_tocopherol.pdf Drug Bank. (2008). Dovonex, viewed 22 March 2009 from http://www.drugbank.ca/search/search?query=davonex FDA issues edentate disodium drug warning (17 January 2008), United Press International, viewed 22 March 2009 from http://www.physorg.com/news119804113.html Hydroxypropyl cellulose (2009) The Free Dictionary, viewed 22 March 2009 from http://medical-dictionary.thefreedictionary.com/Hydroxypropylcellulose Katzung, B.G. (2004). Basic and Clinical Pharmacology (10th edition). London: McGrawHill. Larsen, H. (2008) Fish Oils and Psoriasis, Oil of Pisces, viewed 22 March 2009 from http://209.85.175.132/search?q=cache:3wIzv7HxGpUJ:www.oilofpisces.com/psoriasis.html+liquid+paraffin+psoriasis&cd=1&hl=en&ct=clnk&gl=ph Marty, J., et.al., (November 2005) Rheological properties of three different vitamin D ointments and their clinical perception by patients with mild to moderate psoriasis, Find Health Articles, viewed 22 March 2009 from http://www.find-health-articles.com/rec_pub_16274405-rheological-properties-three-different-vitamin-d-ointments-clinical.htm Marshall, H (12 January 2009) Moisturizers and Moisturizing bath additives or washes, Netdoctor, viewed 22 March 2009 from http://www.netdoctor.co.uk/skin_hair/eczema_moisturisers_003761.htm Medsafe Consumer Information. (2004) DAIVONEX® ointment, cream and scalp solution, viewed 22 March 2009 from http://www.medsafe.govt.nz/Consumers/cmi/d/daivonex.htm Product Information: Daivonex Cream (n.d) health Links, viewed 22 March 2009 from http://secure.healthlinks.net.au/content/csl/pi.cfm?product=cspdaivc11107 Propylene glycol (2009) Encyclopedia Britannica, viewed 22 March 2009 from http://www.britannica.com/EBchecked/topic/479311/propylene-glycol Read More