Dear colleagues; this week we will examine together a gel preparation prescribed in the USA for local anesthetic purposes.
As is known, gels are defined as suspensions of an undissolved hydrated drug in an aqueous medium, with particle sizes approaching or reaching colloidal dimensions. If the particles or molecules in a colloidal dispersion completely entrap the dispersion medium among themselves, the liquid turns into a semi-solid state. This state is called the gel state. Natural (tragacanth gum, pectin, agar), synthetic, or semi-synthetic gums (methylcellulose, carboxymethylcellulose, carbopol) are used in their preparation. Specific types are available for dermatological, ophthalmic, dental, and vaginal use. Local anesthetics reversibly, partially, or completely abolish the ability of all excitable cells (cardiac muscle, striated muscle, smooth muscle, etc.), primarily nerve fibers, to be depolarized (excited) and prevent the propagation of the depolarization wave. This effect of local anesthetics is due to inhibiting the opening of sodium channels in the membrane, thereby decreasing the rapid inward sodium influx. This is the underlying mechanism for temporarily blocking the transmission of painful stimuli from the periphery to the central nervous system (local anesthetic effect).
Formula;
Lidocaine HCL 4 g
Epinephrine HCL 1:1000 injection 50 ml
Tetracaine HCL 0.5 g
Methylcellulose 1500 mPa 10 g
0.9% Sodium Chloride Solution with Parabens qs 100 ml
Substances in the formula;
Lidocaine- Lignocaine- Lidocainum;
Lidocaine is a widely used antiarrhythmic and local anesthetic. Lidocaine is a white to slightly yellowish crystalline powder with a characteristic odor. Its melting point ranges between 66–70°C. It is practically insoluble in water; very soluble in alcohol, chloroform, or methylene chloride; freely soluble in ether; soluble in oils. Lidocaine forms a mixture with prilocaine that has a lower melting point than either component. This eutectic mixture is used in topical dosage forms. Adding 1:200,000 to 1:100,000 epinephrine to a lidocaine solution slows the vascular absorption of the drug and prolongs its effect. When applied topically to mucous membranes, its action begins within 1–2 minutes and lasts for about 30–60 minutes.
Epinephrine hydrochloride- Adrenaline hydrochloride- Suprarenin hydrochloride;
Adrenaline is a creamy-white, odorless, crystalline powder or granular substance. It darkens upon exposure to air and light. According to the British Pharmacopoeia (BP), it is slightly soluble in water; practically insoluble in alcohol and ether. Adrenaline dissolves in mineral acids, sodium hydroxide, and potassium hydroxide solutions; however, it does not dissolve in ammonia and alkali carbonate solutions. According to the United States Pharmacopeia (USP), it is slightly soluble in water and alcohol; insoluble in chloroform, ether, fixed, and volatile oils. Its aqueous solutions show an alkaline reaction to litmus. Neutral and alkaline solutions are unstable and rapidly turn red upon exposure to light.
Adrenaline (epinephrine) is an endogenous catecholamine with therapeutic applications. Endogenous adrenaline is formed primarily from noradrenaline in the adrenal medulla. Adrenaline is administered by injection, inhalation, or topically to the eye; the effects of exogenous adrenaline are identical to those of endogenous adrenaline. Another use is topical ocular application for diagnostic purposes. In addition, it is included in the composition of local anesthetic drug solutions to prolong their duration of action. The effects of adrenaline (epinephrine) on target organs are quite complex. It is a potent agonist acting on both alpha and beta receptors throughout the entire body, except for sweat glands and facial arteries. When applied topically to the skin or mucous membranes, it causes constriction of arterioles, producing vasoconstriction and hemostasis in small blood vessels at the application site.
Amethocaine- Pantocaine- Tetracaine- Tetracainum;
A solid waxy, white or slightly yellowish substance that is poorly soluble in water and soluble in alcohol, ether, and chloroform, tetracaine is an ester-type, long-acting local anesthetic. It is considered the most toxic local anesthetic drug compared to other local anesthetics. These preparations are typically used prior to laryngeal, tracheal, or esophageal examinations to prevent laryngeal and esophageal reflexes and for local analgesia. In addition, it can be used for the palliative relief of pain caused by Herpes labialis. Being a potent local anesthetic, tetracaine is used topically in cream and ointment forms. In dentistry, for occlusion therapy, Tetracaine is prepared in carbomer gel at concentrations of 4% and 1.5%. (Occlusion is defined as any contact or contacts between opposing teeth resulting from the neuromuscular control of the masticatory system.) It must be stored protected from heat and light.
Methylcellulose- Cellulose methyl ether- Methyl ether cellulose- Cologel;
It is attached as a methyl ether to the OH group of cellulose. Methylcellulose is an excipient frequently used in oral and topical pharmaceutical preparations. Methylcellulose is a long-chain substituted cellulose derivative. It exists as white or yellowish-white, hygroscopic, odorless, fibrous granules or powder. It is practically insoluble in hot water, anhydrous alcohol, acetone, chloroform, ether, and toluene; it dissolves in cold water yielding a colloidal dispersion. It also dissolves in glacial acetic acid and equal volumes of an alcohol-chloroform mixture. The pH of its 1% aqueous solution is between 5.5 and 8.0. Methylcellulose solutions are stable between pH 3 and 11 at room temperature. However, its viscosity decreases below pH 3. When its solutions are heated, the viscosity drops once gelation occurs. Incompatibilities of methylcellulose have been reported with chlorocresol, mercuric chloride, resorcinol, tannic acid, silver nitrate, cetylpyridinium chloride, para-aminobenzoic acid, hydroxybenzoates, and phenol. Adding high amounts of electrolytes to methylcellulose solutions causes an increase in the viscosity of the methylcellulose mucilage. However, at very high electrolyte concentrations, methylcellulose may precipitate completely. High amounts cause irritation to the eyes and skin.
Table salt- Sodium chlorure- Natrium chloratum- Natrii hydrochloridum;
Sodium chloride exists as colorless cubic crystals or a white crystalline powder. 1 g of sodium chloride contains approximately 17.1 mmol of sodium and chloride. 2.54 g of sodium chloride is equivalent to approximately 1 g of sodium. It dissolves in water at a ratio of 1:2.8, in boiling water at 1:2.7, and in glycerin at 1:10; it is slightly soluble in alcohol; practically insoluble in anhydrous alcohol. Its 0.9% solution is iso-osmotic. Solutions of some sodium salts, including sodium chloride, may cause particle shedding from glass containers upon prolonged standing over time. Solutions containing such particles should not be used. A 0.9% sodium chloride solution is also known as physiological saline or simply saline.
Preparation of the formula;
Lidocaine and tetracaine are dissolved in the epinephrine solution. To this solution, 0.9% sodium chloride solution with parabens is added to bring the volume to approximately 90 ml. This solution is passed through a 0.22 µm sterile filter into a sterile container, and methylcellulose is sprinkled over it under continuous stirring. To complete the preparation to a volume of 100 ml, 0.9% sodium chloride solution with parabens is added to make up to 100 ml and mixed thoroughly. The preparation should be packaged in syringes containing quantities between 1.5 to 3 ml. However, it must never be administered IM or IV; care must be taken to ensure it is applied topically only.
Usage;
It is used for topical anesthesia purposes, particularly in children, for laceration (tear; wound) repair. The preparation should be stored in the refrigerator in small unit containers. The solution, which is stable at room temperature, can be stored in the refrigerator for 4 weeks. Traditional TAC solutions are applied in liquid form by spreading over the skin and then covering the wound surface with a taped cotton or gauze pad. Prior to this application, after the skin surface is cleansed with an antiseptic agent such as povidone-iodine, the gel is applied. The gel is left on the wound area for approximately 15 minutes or until adequate anesthesia is achieved. The gel is then gently removed with mild soap and water.
Wishing you a good week…
Source;
Allen’s Compounded Formulations
The Complete U.S. Pharmacist Collection
Tel: (332) 3520657
Fax: (332) 3512816
