Lacrisol (Benzalkonium_Hypromellose)
Lacrisol (Benzalkonium_Hypromellose) Uses, Dosage, Side Effects, Food Interaction and all others data.
Benzalkonium chloride is a quaternary ammonium antiseptic and disinfectant. It is also used as an antimicrobial preservative for pharmaceutical products. It is also used for the disinfection of rigid contact lenses.
Benzalkonium chloride solutions are generally categorized as biocidal agents with relative long durations of action. Their spectrum of activity has been demonstrated against bacteria, to some viruses, fungi, and protozoa , although bacterial spores are treated as being resistant to the agent. Additionally, the agent generally shows more activity against gram-positive than gram-negative bacteria . Finally, solutions of benzalkonium chloride are bacteriostatic or bactericidal based on their concentration. Bacteriostatic agents act to prevent further growth of bacterial organisms that are present while bactericidal agents function to kill bacteria that are present . In general, the activity of the agent is not largely affected by pH, but such activity does increase substantially at higher temperatures and prolonged exposure times.
Hydroxypropyl methylcellulose belongs to the group of medicines known as artificial tears. It is used to relieve dryness and irritation caused by reduced tear flow. It helps prevent damage to the eye in certain eye diseases. Hydroxypropyl methylcellulose may also be used to moisten hard contact lenses and artificial eyes. In addition, it may be used in certain eye examinations.
Hypromellose is the most commonly used in hydrophilic matrix fabrication. It allows for controlled release of drug substances, increasing duration of therapeutic effects . The physical characteristics of this drug resemble natural tears, providing lubrication to the ocular surface and maintaining corneal hydration in dry eye syndromes .
Hypromellose is considered an inert substance as it has no direct pharmacological activity. The viscosity promoting properties of hypromellose prolong the retention time and improve adhesion of synthetic tears to the cornea and conjunctiva. As a result, the tear film breakdown time is prolonged and/or the tear film stability is enhanced. A stable tear film protects the cornea from dryness and epithelial cells .
Hypromellose is a methyl and hydroxypropyl mixed ether of cellulose. It is utilized as artificial tears to prevent conjunctival and corneal damage due to impaired lacrimal secretions. It is also used as a visco-elastic promoting agent by maintaining a deep, viscous chamber and allowing for easier manipulation, helping the vitreous surface to be pushed back, thus preventing the formation of a postoperative flat chamber .
| Trade Name | Lacrisol (Benzalkonium_Hypromellose) |
| Generic | Benzalkonium + Hypromellose |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Italy, Taiwan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Higher concentrations of Benzalkonium chloride is used as an antiseptic and disinfectant. This is also widely used as a preservative in eye-drops.
Hypromellose enriched with Carbomer 980 is a long acting eye gel for lubricating the surface of the eye for all patients with ocular discomfort. The slight hypotonicity of the gel is rapidly "neutralised" by the slightly hypertonic tear fluid caused by dry eyes.
Lacrisol (Benzalkonium_Hypromellose) is also used to associated treatment for these conditions: Diaper Dermatitis, Dry Eye Syndrome (DES), Eye and eyelid infections, Gingivitis, Hemorrhoids, Infantile Eczema, Mouth irritation, Pruritus Ani, Tonsillitis, Throat inflammation, Antisepsis, Disinfection therapy, Eye disinfection, Eye lubrication, Hand Hygiene, Skin disinfection, Wound treatmentDry Eyes, Ocular Discomfort, Ocular Irritation
How Lacrisol (Benzalkonium_Hypromellose) works
Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride. .
Promotes corneal wetting by the stabilization and thickening the precorneal tear film and prolonging the tear film breakdown time, which is usually shortened in dry eye conditions. Hypromellose also acts to lubricate and protect the eye .
The surface active properties of the vehicles found in artificial tears solutions act to stabilize the tear film and increase tear viscosity to prevent delay tear evaporation and delay tear drainage .
In the intact eye, the corneal surface is moistened primarily by the mucin that is produced in the conjunctiva. Mucin is adsorbed on the corneal surface and forms a hydrophilic surface. This creates a moisture barrier. In the typical dry eye, and particularly in case of mucin deficiency, the application of artificial tear fluid is highly recommended. Both its surface activity and its adsorptive capacity make hypromellose optimal for this use. Hypromellose has a physical-chemical action and leads to, in an aqueous solution, a reduced surface tension as well as an increased level of viscosity. Hypromellose adheres well to the cornea and conjunctiva and provides ample moisture. Irritation symptoms caused by blinking, which occur in the case of tear fluid deficiency, are therefore decreased and symptoms of epithelial desiccation are also alleviated .
Dosage
Lacrisol (Benzalkonium_Hypromellose) dosage
- Tincture of benzalkonium chloride 1:750 is used for the preoperative disinfection of unbroken skin or treatment of superficial injuries.
- For preoperative disinfection of mucous membranes and denuded skin, benzalkonium chloride solution in concentrations of 1:10000 to 1:2000 is used.
- For irrigation of the eye, a solution of 1:10000 to 1:5000 is used.
- For urinary bladder and urethral irrigation, a solution 1:5000 to 1:20000 is used.
- For vaginal douche and irrigation, benzalkonium chloride solution 1:5000 to 1:20000.
Instill 1 or 2 drops in the conjunctival sac of the affected eye(s), as needed. The frequency of administration depends on the severity of the condition. On average, one drop is administered 1-3 times daily. If needed, Hypromellose may be administered more frequently.
Side Effects
Repeated application may cause hypersensitivity reactions. May cause nausea and vomiting if ingested.
Hypromellose enriched with Carbomer 980 is very well tolerated by users. However, some cases of burning, stinging, allergic reactions or red eyes after instillation have been reported. Transient blurring of vision after administration has also been reported.
Toxicity
An oral dose of 100-400 mg/kg or a parenteral dose of 5-15 mg/kg is believed to be fatal in humans .
A potential concern for larger concentrations of benzalkonium chloride to possibly cause corneal damage when implemented as an excipient ingredient in aqueous eye products is an issue that should be discussed between potential patents and their health care providers . Since decreased regular blinking and tear generation in patients experiencing dry eyes due to any number of eye conditions can result in reduced dilution of applied eye drops containing the benzalkonium chloride preservative , alternative options including benzalkonium chloride-free products should be considered.
Additionally, benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. In addition, benzalkonium chloride may cause eye irritation and is known to discolour soft contact lenses . There may also be the possibility of benzalkonium chloride containing eye drops to cause some stinging and pain .
There is the possibility of ototoxicity occurring when benzalkonium chloride containing ear drops are applied to the ear .
Benzalkonium chloride used as a preservative in nebulised solutions of anti-asthma drugs has been reported to cause dose-related bronchoconstriction especially in asthmatic patients and has been associated with the precipitation of respiratory arrest .
Despite the fairly widespread cutaneous use of benzalkonium chloride, only limited human evidence of sensitization in relatively small populations of individuals have been reported . Nevertheless, the main adverse effect for topical formulations of benzalkonium chloride is usually the warning 'may cause local irritation' .
LD 50 (Rat): > 5 g/kg .
Hypromellose is considered low toxicity to non-toxic .
Adverse events may include blurred vision and contact dermatitis . Hypersensitivity and intolerance reactions may occur (for example, eye burning, pain, increased lacrimation, a sensation of foreign body, conjunctival hyperemia, eyelid swelling, pruritus). The stickiness sensation of the eyelids, the decreased sense of smell, photosensitivity .
Precaution
If eye pains, changes in vision, continued redness or irritation of the eye are noticed Hypromellose must be discontinued and a doctor should be consulted. If Hypromellose changes color or becomes cloudy, the product should not be used.
Interaction
Disinfectants containing quaternary ammonium salts should not be used for skin preparation before injections of viscoelastic solutions. Hyaluronic acid will precipitate in the presence of these salts.
Hypromellose can be used in combination with contact lenses. No compatibility study with lens material is available.
Volume of Distribution
When applied as a topical antibacterial, antiseptic, disinfectant, or sanitizer it is believed that molecules of benzalkonium chloride are poorly absorbed (perhaps due to their large, positively charged nature ), especially considering expectations for such topical applications to keep their biocidal agents available for action at the topical level and to not be absorbed significantly beyond it.
When benzalkonium chloride is implemented as an excipient preservative ingredient in various eye, nose, and ear aqueous products, such products will always have other active pharmacological agents whose volume of distribution will be of greater importance. In these cases the excipients will only ever be present at the minimal levels necessary to maintain the integrity of the product substance.
Moreover, Benzalkonium chloride is currently listed as a Category III ingredient by the United States Food and Drug Administration . Ingredients are listed in the FDA Category III when the data available about them are insufficient to classify as safe and effective, requiring further testing to determine more formal details about elements like human pharmacokinetic studies, and studies on the ingredients' absorption, distribution, metabolism, and excretion.
Elimination Route
Percutaneous absorption is considered to be insignificant .
In one study, benzalkonium chloride absorption was evaluated in women using tampons containing the agent. Venous blood samples were drawn 15 minutes before the tampon application and then again at 15 min, 1 h, 3 h, and 24 h after application. Benzalkonium chloride was not detected in any of the blood samples at any time tested.
Similarly, in another study, benzalkonium chloride absorption was tested in women using tampons containing the agent. Venous blood and breast milk samples were taken 15 minutes before application and 3 h and 24 h after tampon administration. Benzalkonium chloride was not found in any of the subjects' samples. .
Moreover, in a study where benzalkonium chloride solution was placed on the corneal surface of rabbit subjects, at various intervals after administration, the rabbits' eyes would be washed with 1 mL saline and the following tissues and fluids were removed: bulbar and palpebral conjunctiva, aqueous humour, corneal epithelium, endothelium and stroma, iris-ciliary body, lens, vitreous, retina, and choroid. Plasma samples were obtained with direct cardiac punctures. After administration of one drop, benzalkonium chloride was found in the corneal epithelium, endothelium, and stroma, and in the bulbar and palpebral conjunctivae. Benzalkonium chloride loss from ocular tissues was such that about one-third to two thirds of its concentration (depending on the tissue) at 30 min remained after 24 hr; measurable values existed for as long as 120 hr. The administration of multiple drops led to continued accumulation of benzalkonium chloride. .
Not systemically absorbed .
Elimination Route
Administered benzalkonium chloride is likely eliminated largely in faeces, similar to other quaternary ammonium compounds .
Pregnancy & Breastfeeding use
There is no experience regarding the safety of Hypromellose in human pregnancy or lactation. Studies in the pediatric population have not been performed.
Contraindication
Incompatible with soaps and other anionic surfactants, citrates, iodides, nitrates, permanganates, salicylates, silver salts, tartrates, and zinc oxide and sulfate.
Hypersensitivity to this drug or to any ingredient in the formulation or component of the container.
Acute Overdose
No case of overdose has been reported.
Storage Condition
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
Store in a cool dry place, away from light. Keep out of reach of children. Do not touch tip of the tube surface since this may contaminate the gel. After one month of the opening do not use the medicine of tube.
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