- تصييغ وتقييم مستحضر كالسيوم كلوكونيت 2.5 % (وزن/ وزن) كهلام خارجي

Abstract

This work has been carried out to formulation and evaluation pharmaceutical product containing calcium gluconate (2.5 % w/w) as topical gel, which is indicated in burns of hydrofluoric acid exposure to the body. Different formulations were prepared using variable gel bases، preservatives and humectants . Selection of best formula relied solely on physic-chemical testing of sample exposed to thermal stresses. The stability study was conducted on the product for (6) months at different temperatures (40، 50 and 60) ◦C to determine the expiration date and the best storage conditions. The study revealed gel of good homogeneity, softness and adhesivity . Expiry date with an not less than (2) years.

Keywords :- calcium gluconate ، gel، hydrofluoric acid burn .

Introduction Hydrofluoric acid (HFA) is a highly corrosive chemical agent that can cause severe and deep burns on exposure by viable tissues. It is imperative that medical assistance be provided for any exposure to (HFA) and the treatment be initiated promptly. Hydrofluoric acid differs from other corrosive chemicals in that the fluoride ion readily penetrates the skin causing destruction of deep tissue layers including bone. However, its critical harmful effect comes from the action of the fluoride ion (F-), not acid burn. Fluoride iron from (HFA) forms such a strong bond to Ca2+ in bones. It reaches to bones and leaches calcium from bones and may tie up calcium in nerve cell. This disruption of nerve condition can be life threatening when disrupting a heart function [1] . Hydrofluoric acid is a toxic substance used widely in both industrial and domestic settings. It can cause severe burns, as well as systemic toxicity. Death has been reported from as little as (2.5%) body surface area (BSA) burn involving concentrated acid . Topical and parenteral calcium salts have proven effective therapy for both dermal and systemic manifestations [2] . Calcium gluconate gel is an effective topical (2.5%) calcium gluconate that is used in first aid response to hydrofluoric acid (HFA) exposure or contact to the body [3] . Calcium gluconate White or almost white, crystalline or granular powder. Sparingly soluble in water, freely soluble in boiling water [4] . Experimental work Several formulations with different gel bases (carbomer 940, carboxy methyl cellulose sodium (Na CMC), hydroxyl propyl methyl cellulose (HPMC) were prepared and selected the best formula . The best formula contains ingredients are presented in table (1). In suitable Pyrex beaker boil distilled water then dissolve the following materials , methyl paraben , propyle paraben , in another Pyrex beaker dissolve carbomer (940) in distilled water then add propylene glycol and stirred until a homogenous gel was achieved , in another beaker mix calcium gluconate and glycerin , mix well then mix all beakers with starring for (15 min) or until clear gel formed, complete the weight to (100 g) with distilled water , cool to ( 25 ◦ C) , check the pH; it should be between (5 – 7) , fill in (50 g) aluminum lacquer tube

Table -1- list of ingredients Item no. ingredients Quantity 1. 2. 3. 4. 5. 6. Calcium gluconate . Carbomer 940 Methyl paraben (M.P) Propyle paraben (P.P) Propylene glycol Glycerin 2.5 g 3 g 0.1 g 0.05 g 10 g 15 g

Stability study : Stability study was conducted on the product for ( 6 ) months at different temperatures (40 ،50، 60) ◦C to determine the expiration date and the best storage conditions .

Results and Discussion A homogenous colorless viscous gel was obtained and the physico – chemical properties of it is presented in table (3) .On the other hand , stability studies is presented in table (4) . In this study, different formulas of gel were prepared according to the specification of united state pharmacopeia. Carbomer )940( showed best gelling agent than (Na CMC) and (HPMC). A homogenous colorless gel of acceptable consistency was produced with excellent stability at different temperatures (40, 50, and 60) ◦C. According to this study, the expiration date has been estimated to be not less than (2) years from the date of manufacturing at room temperature.

Table -2- Quantitative composition of calcium gluconate gel Formulations (% w/v). Formula no. Calcium gluconate Carbomer 940 Propylene glycol Na CMC HPMC Glycerin M.P P.P 1 2.5 3 10 --- --- 15 0.1 0.05 2 2.5 3 10 --- 8 15 0.1 0.05 3 2.5 3 10 3 --- 15 0.1 0.05 4 2.5 3 10 2.5 8 15 0.1 0.05 5 2.5 3 10 3 9 15 0.1 0.05 * Distilled water was added to make up to 100 gm of each gel

Table- 3- Rheological , physical and chemical properties of calcium gluconate gels for different formulations .

Formula no. viscosity (centipoise) pH Drug Content Homogeneity Spreadability Glycerin M.P P.P 1 2000 6.35 103.3 yes Easy 15 0.1 0.05 2 1720 6.3 103.2 Yes Easy 15 0.1 0.05 3 1709 6.3 102.6 no Easy 15 0.1 0.05 4 1940 6.25 103.2 yes Easy 15 0.1 0.05 5 1980 6.27 103.4 no Easy 15 0.1 0.05

Table -3-The physic – chemical changes of calcium gluconate gel 2.5%w/w with time at different temperatures.

Storage time (month) Temp. ◦ C % of calcium gluconate pH (5-7) appearance Zero time 25 103.63 6.35 colorless Homogenous gel 1 40 103.5 6.34 colorless Homogenous gel 50 103.42 6.32 colorless Homogenous gel 60 103.31 6.30 colorless Homogenous gel 2 40 103.39 6.33 colorless Homogenous gel 50 103.31 6.31 colorless Homogenous gel 60 103.2 6.00 colorless Homogenous gel 3 40 103.28 6.31 colorless Homogenous gel 50 103.2 6.30 colorless Homogenous gel 60 103.09 6.28 colorless Homogenous gel 4 40 103.17 6.28 Pale yellow Homogenous gel 50 102.95 6.27 Pale yellow Homogenous gel 60 102.98 6.25 Pale yellow Homogenous gel 5 40 102.96 6.25 Pale yellow Homogenous gel 50 102.92 6.24 Pale yellow Homogenous gel 60 102.91 6.22 Pale yellow Homogenous gel 6 40 102.81 6.22 Pale yellow Homogenous gel 50 102.87 6.19 Pale yellow Homogenous gel 60 102.85 6.15 Pale yellow Homogenous gel

Table -4- The T90% at different temperature.

T90% Year T90% day Temp. 3 1095 R.T◦C 2.5 912 40◦C 2.3 839 50◦C 1.9 693 60◦C

References 1- M.A. Trevino et al, HF Exposure Treatment Guide for Physicians, University of Southern California Environmental Health and Safety, J. Occ Med., 25, p. 861, 2014. 2- Bertolini JC, Hydrofluoric acid: a review of toxicity, J Emerg Med. 1992 Mar-Apr;10(2):163-8. 3-Source: Segal, Eileen, B “First Aid for a Unique Acid, HF: A Sequel” Chemical Health and Safety, Jan/Feb 2000 vol. 7, #1, p18. 4-British Pharmacopoeia press, 2013, British Pharmacopoeia , U.K. 5- Kim Huynh , (2009),Accelerating aging, Handbook of stability testing in pharmaceutical development , springer ,USA .

الخلاصة نفذ هذا العمل لتطوير منتج صيدلاني يحتوي على غلوكونات الكالسيوم (2.5٪ وزن / وزن) كهلام موضعي ، والتي تعالج الحروق الناتجة من تعرض الجسم لحمض الهيدروفلوريك . حضرت تركيبات مختلفة باستخدام قواعد هلام متغيرة ، مواد حافظة ومغذيات . اختيرت أفضل تركيبة بالاعتماد على الاختبارات الفيزيائية والكيميائية للعينة المعرضة للضغوط الحرارية. أجريت دراسة الثباتية على المنتج لمدة (6) أشهر في درجات حرارة مختلفة (50،40،25 و60( م◦ لتحديد تاريخ انتهاء الصلاحية وأفضل ظروف التخزين . وكشفت الدراسة هلام جيد التجانس ، الليونة والالتصاق. تاريخ انتهاء الصلاحية لا يقل عن سنتان .