Boric acid suppository in the treatment of vulvovaginitisDear Colleagues, this week we will briefly examine together a suppository preparation used in the treatment of inflammation of the vulva and vagina in the United States.
Vaginitis is an inflammation of the vaginal mucosa and one of the most common reasons for visits to gynecologists. Vaginitis affects 90% of women from puberty onwards, and in 30% of cases, two or more infections co-occur1,2,3.
Vaginal discharge is normally a clear, egg-white-like secretion that keeps the vaginal environment moist. Under natural conditions such as pregnancy, sexual arousal, and ovulation, vaginal secretions may increase, but this is normal and does not cause any complaints. For this reason, an increase in vaginal discharge does not always indicate a sign of disease.
If an increase in the amount of vaginal discharge, accompanied by changes in its color and consistency, is associated with itching, burning, and a foul odor, and especially if these symptoms last for more than 2–3 days, vaginal discharge may indicate the presence of a problem.
Vaginitis is generally not a life-threatening condition. However, if not treated promptly and properly, it can lead to more serious health problems.
Three causative agents are frequently (90%) responsible for the occurrence of vaginitis:
– Fungi (Candida albicans)
– Bacteria (Gardnerella vaginalis)
– Parasites (Trichomonas vaginalis)
Apart from these, bacteria of the Chlamydia and Mycoplasma groups, Neisseria gonorrhoeae, Escherichia coli, Giardia lamblia, Balantidium coli, Entamoeba histolytica, and Ureaplasma urealyticum are microorganisms that may be responsible for the clinical presentation of vaginitis4.
Leading the factors that play a role in the development of vaginitis are the disruption of the normal vaginal environment (flora) and changes in pH.
When two or all of these causative agents occur together, they are referred to as mixed vaginal infections.
The most common types of vaginitis are candidal vulvovaginitis caused by fungi, bacterial vaginosis caused by bacteria, and trichomonal vaginitis caused by parasites.
The causative agent of candidal vulvovaginitis, a common type of vaginitis, is predominantly the yeast fungus known as Candida albicans. Candida albicans is the most prominent fungus found on the skin, mucous membranes, and normal flora of healthy individuals that causes infection as a result of the disruption of the organism’s natural resistance. This type of vaginitis occurs at least once in a lifetime in approximately 75% of adult women, and recurs two or more times in 40-50% of them.1.Symptoms of Candidal Vulvovaginitis;Its primary symptom is severe itching and irritation around the vagina. In addition, redness and swelling of the external genitalia, as well as a thick and scanty, curd-like (cottage cheese-like) discharge are also present.2.
Normally found in the flora of the mouth, throat, intestines (colon), and vagina, this fungus causes disease under conditions that alter the body’s balance, such as pregnancy, diabetes, obesity, as well as with the use of birth control products, spermicides, intrauterine devices (IUDs), and intensive antibiotic use.5.
In the treatment of these infections, products known as antifungals, administered orally or vaginally against fungi, are used.Factors Facilitating the Development of Vaginitis;– Wearing tight synthetic clothing
– Pregnancy (changes in hormonal balance)
– Diabetes
– Use of birth control pills
– Improper hygiene practices
– Immune system deficiency are among the factors that facilitate the development of vaginitis.Precautions to be Taken to Prevent Vaginitis;Hygiene is a fundamental factor in disease prevention. Changing underwear daily and boiling and ironing them is beneficial.
Frequent washing of the vagina with soap or intimate washes disrupts the protective layer of the vagina, predisposing it to inflammatory diseases. Prolonged use of tampons and pads is also an adverse factor.
Public baths and excessively chlorinated pools should be avoided; public toilets and shared toilet cleaning materials should not be used.
For external genital hygiene, washing and drying should be done from front to back. This technique prevents the transfer of microbes from the perianal area, which is rich in microorganisms, to the vagina.
Clothing choice is an important factor in disease prevention. Synthetic fiber underwear and tight, restrictive clothing such as tight trousers promote fungal growth, in particular, because they allow poor ventilation and increase the temperature and humidity around the vagina. Garments that remain wet for extended periods, such as swimwear, are harmful for the same reason. Therefore, comfortable clothing and cotton underwear should be preferred.
Chemical contact may alter the vaginal environment as a result of local allergy and hypersensitivity, leading to vaginitis. For this reason, the use of scented toilet paper should be avoided.
Because prolonged and uncontrolled antibiotic use is a common cause of vaginitis, antibiotics should only be taken under medical supervision.
Dietary habits may also be a predisposing factor for vaginitis. In particular, a diet high in sugar can increase blood glucose levels, facilitating the onset of the condition.
Because irritation resulting from sexual intercourse can facilitate the development of infections, and pain is a common finding across all types of vaginitis, sexual intercourse should also be avoided throughout the course of treatment for other forms of vaginitis.Boric acid suppository in the treatment of chronic vulvovaginitis;
Rp.
Boric Acid 600.0 mg
Polyethylene Glycol Base 1.71 g
Polyethylene Base formula;
Rp.
Polyethylene Glycol 1000 65%
Polyethylene Glycol 4000 35%
Or
Polyethylene Glycol 400 60%
Polyethylene Glycol 8000 40%
Substances in the formula;
Boric acid- Acide borique [DCF; FP]- Acido borico [FU]- Boric acid [BP; INCI; NF; P.Cx.79];Boric acid is a medication with weak bacteriostatic and fungistatic activity. It is used topically. Its ophthalmic preparations are used in the treatment of ocular irritation and inflammation. Its topical preparations are useful in soothing irritated skin, skin abrasions, burns, and other cases of skin irritation. Vaginal candidiasis caused by Candida glabrata and other non-albicans species often responds favorably to topical boric acid therapy. Topically applied boric acid preparations may cause systemic toxicity, especially when the skin is damaged. Its current use has lost its former significance due to the availability of more effective and less toxic drugs. In eye drops, it is frequently used with borax for its buffering and antimicrobial effects. CAUTION! Neither boric acid nor borax should be used for systemic effect (internally).
CAUTION! Pharmacists are advised not to dispense powdered boric acid to patients. Due to the risk of toxicity, powder preparations containing more than 5% boric acid should not be applied to abraded, broken, or weeping skin surfaces. Boric acid preparations should not be used in infants and young children.
Boric acid is a weak topical anti-infective agent with fungistatic and bacteriostatic properties. The exact mechanism of boric acid’s antibacterial and antifungal effects is not known. Boric acid demonstrates a slow bacteriostatic effect against staphylococci and streptococci. Its action in the vagina is thought to depend on increasing vaginal pH. The increase in vaginal pH enhances penetration through the fungal cell wall and causes disruption of the cell wall structure.
Applied as a mild antiseptic to an inflamed eye (e.g., in the form of a solution or ointment), boric acid exhibits weakly acidic properties and is frequently used for its antiseptic effect. It impairs cell membrane permeability by causing coagulation of bacterial cell wall proteins. While its 5% aqueous solutions exhibit phagocytic activity, its 2-4% solutions prevent the proliferation and growth of bacteria.
When accidentally ingested via the oral route, boric acid causes acute poisoning. Nausea, diarrhea, abdominal pain, erythematous rash, and desquamation on the skin and mucous membranes may be observed. Stimulation or depression may occur in the CNS. Convulsions and hyperpyrexia may be seen. It can cause renal tubular necrosis. Death occurs within 3–5 days due to circulatory collapse and shock. With repeated use, it can accumulate cumulatively and cause chronic toxicity due to its slow elimination from the body. Symptoms of chronic poisoning include anorexia, gastrointestinal disturbances, debility, confusion, dermatitis, menstrual disorders, anemia, convulsions, and alopecia. Fatal cases have been reported, especially in young children, due to accidental ingestion of boric acid solutions or application to large areas of damaged skin. Therefore, boric acid preparations should not be used in infants and young children. It is recommended that boric acid does not exceed a concentration of 5% in talc and 0.5% in preparations used for oral hygiene. Talcum powders containing boric acid should not be used in children under 3 years of age. Preparations containing boric acid should not be applied to extensive areas of damaged or abraded skin. Irrigation of body cavities with boric acid-containing preparations is no longer recommended due to the risk of toxicity. Boric acid and borax are substances that cause pulmonary irritation when inhaled. Treatment of poisoning is symptomatic.
Boric acid is absorbed from the gastrointestinal tract (when ingested accidentally), damaged skin, wounds, and mucous membranes. It is not readily absorbed when applied topically to intact skin. Approximately 50% of the absorbed amount is excreted in the urine within 12 hours, while the remainder is excreted within 5–7 days.
Boric acid occurs as odorless white crystals or shiny flakes, or as a white crystalline powder that feels unctuous to the touch. When heated to 100°C, it loses water and slowly converts to metaboric acid (HBO2). When heated at 140°C, it converts to tetraboric acid (H2B4O7) and when heated at higher temperatures, to boron trioxide (B2O3). It is soluble 1:20 in water, 1:3.6 in boiling water, 1:16 in alcohol, 1:6 in boiling alcohol, and 1:4 in glycerin (85%). Boric acid forms a complex with glycerin that is more acidic than when it is on its own. The pH of a 3.3% solution in carbon dioxide-free water is between 3.8 and 4.8. Aqueous solutions should be stored in tightly closed containers.
When applied topically, these solutions are known to have greater bacteriostatic activity compared to formulations containing an oily base (cream/ointment).Polyethylene glycols- Macrogol- Carbowax- Polyoxyethylene glycols;Polyethylene glycols are water-soluble bases used in topical preparations and suppositories. They are also used as solvents, vehicles, solubility enhancers, tablet binders and lubricants, and as plasticizers in film tablet coating. Some types, such as Macrogol 3350, are used orally in combination with electrolytes as laxatives. Polyethylene glycols are condensation products of ethylene oxide and water. Polyethylene glycols with an average molecular weight between 200–600 are clear, colorless, or slightly yellow viscous liquids. They are substances with a faint characteristic odor and a bitter taste. Polyethylene glycols with an average molecular weight over 1000 are white or off-white solids of varying consistency or powders. They have a faint characteristic odor. While their viscosity increases with increasing molecular weight, their hygroscopicity decreases. For example, PEG 4000 and higher polyethylene glycols are not hygroscopic. All polyethylene glycols are water-soluble and miscible with each other in all proportions. Liquid types are soluble in acetone, alcohols, benzene, glycerin, and glycols. Solid types are soluble in acetone, dichloromethane, ethanol, and methanol; sparingly soluble in aliphatic hydrocarbons and ether; practically insoluble in fixed oils and liquid paraffin. High-molecular-weight types such as Polyethylene glycol 20,000 form gels in aqueous solutions.
Polyethylene glycol suppository bases are very popular because they are water-soluble and easy to use. They have excellent stability and, by melting/dissolving in the vaginal or rectal cavity, easily mix with body fluids to deliver active ingredients.Preparation of the formulation;Ingredients are weighed or measured. The polyethylene glycol mixture is melted at 60-70 °C. The particle size of the boric acid is reduced to a fine powder. Boric acid powder is added to the melted polyethylene base and mixed thoroughly. It is cooled by a few degrees and poured into a suppository mold at room temperature. Allowed to stand until hardened. Suppositories are placed in a suitable package and labeled.
PEG suppository base can be prepared by melting high-molecular-weight PEG 4000 or PEG 8000. PEG 1000 or PEG 400 is added, melted, and mixed thoroughly. It should be stored in a cool place.Directions for use;Boric acid vaginal suppository is used in the treatment of chronic mycotic vulvovaginitis.
Storage; Package in airtight, light-resistant containers. It should not be packaged in polystyrene containers.
Must be labeled for vaginal use only. Used in accordance with recommendations. The prescribed dose should not be exceeded and it must be kept out of the reach of children.
Stability; Must be consumed within 6 months from the date of manufacture.The majority of patients with mycotic vulvovaginitis respond well to new antifungal agents; however, in cases presenting as recurrent or persistent infections, and in the treatment of patients who previously did not respond to commonly used antifungal agents, boric acid has been shown to have a 98% cure rate.A 600 mg boric acid suppository is administered vaginally twice daily.
It is also interesting that the combination of boric acid with a vaginal contraceptive (nonoxynol-9) may have antagonistic effects. As a result, vaginal contraceptives should not be used concurrently with boric acid vaginal suppositories.
Wishing you a good week…References;1- Egan, ME, Lipsky, MS. Diagnosis of Vaginitis; American Family Physician, 2000 Sep 1; 62(5): 1095-104.
2- Hetal B Gor, Vaginitis: Differential Diagnoses & Workup. Updated: May 19, 2010.
3- Coco AS, Vandenboscheet M. Postgraduate Medicine, 2000, 107: No.4: 63-74.
4- Family Practice News. A Clinical Update In Treatment of Bacterial Vaginosis.
5- Mardh, PA., Tchoudomirova, K., Elshiby, S., Hellberg, D. Symptoms and signs in single and mixed genital infections. Int. J Gynecol Obstet 1998; 63: 145-152.
6- Balcı O, Çağar M.: Vaginal infections. Journal of the Turkish Society of Obstetrics and Gynecology, 2005; Volume: 2 Issue: 5 Pages: 14-20.
7- Jack D. Sobel. Vaginitis. The New England Journal of Medicine. December 25th, 1997.
8- Sexually Transmitted Diseases Treatment Guidelines, 2006, MMWR.
9- Allen’s Compounded Formulations
10- RxMediaPharma®2016 Interactive Drug Information Resource
Spec. Pharm. Ahmet Nezihi Pekcan
Pekcan Pharmacy – Konya
[email protected]
Tel: (332) 3520657http://www.majistralformul.com/
