PHARMACEUTICAL PREPARATIONS

OTIC PREPARATIONS (ear)
SUPPOSITORIES
VAGINAL SUPPOSITORIES
VAGINAL SOLUTIONS
ENEMAS

1. PHARMACEUTICAL PREPARATIONS Dr. Asra Hameed Pharm.D (JUW) [email protected]

2. INTRODUCTION

3. OTIC PREPARATIONS SUPPOSITORIES VAGINAL SUPPOSITORIES VAGINAL SOLUTIONS ENEMAS TOPICS

4. Otic preparations are sometimes referred to as ear or aural preparations . Solutions are most frequently used in the ear, with suspensions and ointments also finding some application. Ear preparations are usually placed in the ear canal by drops in small amounts for removal of excessive cerumen (earwax) or for treatment of ear infections, inflammation, or pain . Otic Preparations

5. The auricle is the opening to the ear ; The ear lobe surrounds the auricle ; The external auditory canal starts at the auricle and ends at the tympanic membrane Ear Physiology

6. Cerumen is a combination of the secretions of the sweat and sebaceous glands of the external auditory canal. The secretions, if allowed to dry, form a sticky semisolid that holds shed epithelial cells, fallen hair, dust, and other foreign bodies that make their way into the ear canal. Excessive accumulation of cerumen in the ear may cause itching, pain, and impaired hearing, and it impedes otologic examination. If not removed periodically, the cerumen may become impacted and its removal made more difficult and painful. Through the years, light mineral oil, vegetable oils, and hydrogen peroxide have been commonly used agents to soften impacted cerumen for its removal. Recently, solutions of synthetic surfactants have been developed for their ability to remove earwax. One commercial product uses carbamide peroxide in glycerin and propylene glycol ( Debrox Drops, Murine Ear). On contact with the cerumen , the carbamide peroxide releases oxygen, which disrupts the integrity of the impacted wax, allowing its easy removal. Cerumen removal usually involves placing the otic solution in the ear canal with the patient’s head tilted at a 45° angle, inserting a cotton plug to retain the medication in the ear for 15 to 30 minutes, followed by gentle flushing of the ear canal with lukewarm water using a soft rubber ear syringe. Cerumen -removing Solutions

7. OTIC PREPARATIONS

8. Drugs used topically in the ear for their anti-infective activity include such agents as ciprofloxacin,, colistin sulfate, neomycin, ofloxacin, polymyxin B sulfate, and nystatin, the latter agent used to combat fungal infections. These agents are formulated into eardrops (solutions or suspensions) in a vehicle of anhydrous glycerin or propylene glycol. These viscous vehicles permit maximum contact time between the medication and the tissues of the ear . In addition, their hygroscopicity causes them to draw moisture from the tissues, reducing inflammation and diminishing the moisture available for the life process of the microorganisms. To assist in relieving the pain that frequently accompanies ear infections, a number of anti-infective otic preparations also contain analgesic agents, such as antipyrine , and local anesthetics, such as pramoxine hydrochloride and benzocaine . Topical treatment of ear infections is frequently considered adjunctive, with concomitant systemic treatment with orally administered antibiotics. Anti-infective, Anti-inflammatory, and Analgesic Ear Preparations

9. Liquid ear preparations of the anti-inflammatory agents hydrocortisone and dexamethasone sodium phosphate are prescribed for their effects against the swelling and inflammation that frequently accompany allergic and irritative manifestations of the ear and for the inflammation and pruritus that sometimes follow treatment of ear infections . In the latter instance, some physicians prefer the use of corticosteroids in ointment form, packaged in ophthalmic tubes. These packages allow placement of small amounts of ointment in the ear canal with a minimum of waste. Many commercial products used in this manner are labeled eye and ear to indicate their dual use . Anti-infective, Anti-inflammatory, and Analgesic Ear Preparations

10. Aside from the antibiotic–steroid combinations that are used to treat otitis externa , or swimmer’s ear, acetic acid 2% in aluminum acetate solution and boric acid 2.75% in isopropyl alcohol are used. These drugs help to reacidify the ear canal, and the vehicles help dry the ear canal. Drying the ear canal keeps in check growth of the offending microorganisms, usually P. aeruginosa . Pharmacists may also be called on for extemporaneous preparation of a solution of acetic acid 2% to 2.5% in rubbing alcohol (70% isopropyl alcohol or ethanol), propylene glycol, or anhydrous glycerin. The source of the acetic acid can be Glacial Acetic Acid, USP, or Acetic Acid, NF. Boric acid 2% to 5% dissolved in either ethanol or propylene glycol has also been recommended for use in the ear. This substance, however, may be absorbed from broken skin and be toxic. Thus, its use is usually limited, especially in children with burst eardrums . Anti-infective, Anti-inflammatory, and Analgesic Ear Preparations

11. Pain in the ear frequently accompanies ear infection or inflamed or swollen ear tissue. Frequently, the pain is far out of proportion to the actual condition. Because the ear canal is so narrow, even a slight inflammation can cause intense pain and discomfort. Topical analgesic agents generally are employed together with internally administered analgesics, such as aspirin, and other agents, such as anti- infectives , to combat the cause of the problem. Most topical analgesics for the ear are solutions, and many contain the analgesic antipyrine and the local anesthetic benzocaine in a vehicle of propylene glycol or anhydrous glycerin ( Antipyrine 54 mg, Benzocaine 14 mg, Dehydrated glycerin qs 10 mL). Again , these hygroscopic vehicles reduce the swelling of tissues (and thus some pain) and the growth of microorganisms by drawing moisture from the swollen tissues into the vehicle. These preparations are commonly employed to relieve the symptoms of acute otitis media. Anti-infective, Anti-inflammatory, and Analgesic Ear Preparations

12. As determined on an individual product basis, some liquid otic preparations require preservation against microbial growth. When preservation is required, such agents as chlorobutanol 0.5%, thimerosal 0.01%, and combinations of the parabens are commonly used. Antioxidants , such as sodium bisulfite, and other stabilizers are also included in otic formulations as required. Ear preparations are usually packaged in 5- to 15-mL glass or plastic containers with a dropper. Anti-infective, Anti-inflammatory, and Analgesic Ear Preparations

13. OTIC PREPARATIONS

14. Subtle differences in the formulation of otic suspensions may be bothersome to the patient. This is so especially as it relates to differences in inactive or inert ingredients that are considered equivalent on the basis of active ingredients and strength. For example, several suspension combinations of polymyxin B sulfate, neomycin sulfate, and hydrocortisone have been shown to be more acidic at pH 3.0 to 3.5 than the standard product, Cortisporin -TC Otic (Monarch), whose pH is 4.8 to 5.1. Consequently, there is a risk that when drops are legally substituted, a burning and stinging sensation can occur when the drops are introduced into the ear of young children, especially those with tympanostomies . It has also been demonstrated that with time, the pH of these formulations, including Cortisporin , becomes more acidic, possibly pH 3.0. Thus, if it is stored over time, the acidity may irritate the ear canal on later use. For this reason, this antibiotic–hydrocortisone combination has been formulated into a new suspension product, PediOtic ( Glaxo Wellcome ), with a minimum pH of 4.1. Otic Suspensions

15. When eardrops are prescribed, it is important for the pharmacist to determine how the drops are to be used. For example, earwax removal drops should be instilled and then removed with an ear syringe. Drops intended to treat external otitis infection are intended to be instilled and left in the ear. The pharmacist should make sure the child, parent, or caregiver understands that administration is intended for the ear and the frequency of application. To facilitate acceptance, the pharmacist should point out that the bottle or container of medication should first be warmed in the hands, and if the product is a suspension, shaken prior to withdrawal into the dropper. The pharmacist should also explain the need to store the medication in a safe place out of the reach of children and away from extremes of temperature. When instilled into the ear, to allow the drops to run in deeper, the earlobe should be held up and back. For a child, the earlobe should be held gently down and back. For convenience, it is probably easier to have someone other than the patient to administer the drops . Proper Administration and Use of Otic Drops

16. Some eardrops by virtue of their low pH may cause stinging upon administration. Parents and children should be forewarned, especially if a child has tympanostomy tubes in the ear. The patient or parent should also understand how long to use the product. For antibiotic eardrops it is not necessary to finish the entire bottle, because therapy could last 20 to 30 days, depending upon the dosage regimen. Therefore, patients should be instructed to continue using the drops for 3 days after symptoms disappear. Products for otitis externa may take up to 7 to 10 days to demonstrate efficacy. If a child is prone to develop ear infections as a result of swimming or showering, it might be advisable to recommend the parents to consult a physician for prophylactic medication to use during swimming season and consider using ear plugs that fit snugly in the ear when swimming or showering. After the child emerges from the water or shower, the parents can be advised to use a blow dryer on a low setting to dry the ear quickly without trauma. The dryer should not be held too close to the child’s ear . Proper Administration and Use of Otic Drops

17. SUPPOSITORIES & SUPPOSITORY BASES

18. A suppository is a drug delivery system that is inserted into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository), where it dissolves or melts and is absorbed into the blood stream. They are used to deliver both systemically and locally acting medications. Suppositories

19. Suppository bases may be conveniently classified as according to their composition and physical properties: Oleaginous (fatty) bases Water soluble or miscible bases Suppository bases

20. Water soluble/water miscible bases are those containing glycerinated gelatin or the polyethylene glycol (PEG) polymers. Glycerinated Gelatin Suppositories Glycerinated Gelatin is a useful suppository base, particularly for vaginal suppositories. It is suitable for use with a wide range of medicaments including alkaloids, boric acid, and zinc oxide. Glycerinated gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in mucous secretions to provide prolonged release of active ingredients.it is may be prepared by dissolving granular gelatin (20%) in glycerin (70%) and adding water or solition or suspension of medication (10%) Water Soluble/Water Miscible Bases:

21. Fatty bases are perhaps the most frequently employed suppository bases, principally because cocoa butter is a member of this group of substances. Among the other fatty or oleaginous materials used in suppository bases are many hydrogenated fatty acids of vegetable oils, such as palm kernel oil and cottonseed oil. Also, fat-based compounds containing compounds of glycerin with the higher–molecular-weight fatty acids, such as palmitic and stearic acids, may be found in fatty bases. Such compounds, such as glyceryl monostearate and glyceryl monopalmitate , are examples of this type of agent. Fatty or Oleaginous Bases

22. SUPPOSITORIES MANUFARTURING

23. Method of Manufacturing of Suppositories Suppositories can be extemporaneously prepared by one of three methods. 1. Hand Rolling:   it is the oldest and simplest method of suppository preparation . 1. The drug is made into a fine powder. 2. It is incorporated into the suppository base by trituration in a mortar. 3. Then the incorporated mass is rolled between fingers into rod shaped units. 4.The mass is formed into a ball in the palm of the hands. 5. then rolled into a uniform cylinder with a large spatula. 6.The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape. Effective hand rolling requires considerable practice and skill. The suppository "pipe" or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded and softened.

24. 2. Compression Molding it  is a method of preparing suppositories from a mixed mass of grated suppository base and medicaments which is forced into a special compression mold . In preparation for compression into the molds. the base and the other formulative ingredients are combined by thorough mixing. the friction of the process softening the base into a pastelike consistency. On a small scale, a mortar and pestle may be used. Heating the mortar in warm water (then drying it) greatly facilitates the softening of the base and the mixing. On a large scale, a similar process may be used, employing mechanical kneading mixers and a warm mixing vessel .

25. 3. Fusion Molding  : It involves: first melting the suppository base, and then dispersing or dissolving the drug in the melted base. The mixture is removed from the heat and poured into a suppository mold. When the mixture has congealed, the suppositories are removed from the mold. The fusion method can be used with all types of suppositories and must be used with most of them.

26. VAGINAL SUPPOSITORIES & PACKAGING & STORAGE

27. These prep are used to control infections in female genitourinary tract , to restore vaginal mucosa and for contraception . The most common used base for v.suppositories consist of combination of various molecular wt. Polyethylene glycol nd to this surfactants and preservatives are added. Vaginal suppositories

28. Wash your hands thoroughly before administering the suppository. Remove the foil wrapper and moisten the suppository with water or water-based lubricating jelly. Lie on your back with your knees bent. Hold the applicator in one hand. Put the applicator into your vagina (like you would a tampon) as far as you can. Slowly press the plunger until it stops. Withdraw the applicator. The medicine will be left behind in the vagina. Please lie for 10-15 min after insertion to ensure absorption of medication. Wash the applicator with soap and water after every use, rinsing and drying it well. While using this medicine, wear a sanitary pad to protect your underwear. Vaginal Suppository (with the applicator )

29. packed in plastic boxes glycerin and glycerinated gelatin supp. are packed in tightly closed glass containers cool place. oleogenous suppositories should be place at 30c glycerinated gelatin at 20-25c. Packaging and storage

30. VAGINAL SOLUTIONS

31. VAGINAL DOUCHES: powders are used to prepare solution for vaginal douche that is for irrigation, cleansing of the vagina. The powder them selves may be prepared and packed in bulk or as unit packages. Among the components of double powder are the following: Antiseptic ( Na borate) Astringent (K, Zn sulphate) Antimicrobial (povidone iodine) Detergent (Na lauryl sulphate) Oxidizing agent ( Na perporate) Salts (NaCl, Na citrate) Aromatics (menthol, Eucalyptus) VAGINAL SOLUTIONS

32. ENEMAS

33. An enema is the procedure of introducing liquids into the rectum and colon via the anus. The increasing volume of the liquid causes rapid expansion of the lower intestinal tract, often resulting in very uncomfortable bloating, cramping, powerful peristalsis, a feeling of extreme urgency and complete evacuation of the lower intestinal tract. An enema has the advantage over any laxative in its speed and certainty of action, and some people prefer it for this reason. Enemas can be carried out as treatment for medical conditions, such as constipation and as part of some alternative health therapies. They are also used to administer certain medical or recreational drugs. Enemas have been used for rehydration therapy ( proctoclysis ) in patients for whom intravenous therapy is not applicable. Enema

34. The main medical usages of enemas are : * As a bowel stimulant, laxative – * Enemas may also be used to relieve constipation and fecal impaction, although in the U.S.A. and some other parts of the world, their use has been replaced in most professional health-care settings by oral laxatives and laxative suppositories. * Bowel stimulating enemas usually consist of water, which works primarily as a mechanical stimulant, or they may be made up of water with baking soda (sodium bicarbonate) or water with a mild hand soap dissolved in it. * Cleansing the lower bowel prior to a surgical procedure such as colonoscopy. * The administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as antiemetics given to reduce nausea ( though not many antiemetics are delivered by enema). Medical usage:

35. * Additionally, several anti- angiogenic agents, which work better without digestion, can be safely administered via a gentle enema. Medicines for cancer, for arthritis, and for age-related macular degeneration are often given via enema in order to avoid the normally-functioning digestive tract. Interestingly, some water-based enemas are also used as a relieving agent for irritable bowel syndrome, using in the colon and rectal area. Finally, an enema may also be used for hydration purposes. . * Administration by enema avoids having the medication pass through the entire gastrointestinal tract, therefore simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream. * enema., anesthetic agents are used rectally to reduce medically induced vomiting during and after surgical procedures, in an attempt to avoid aspiration of stomach contents. Medical usage:

36. Cleansing enema : Cleansing enema: (high): Given to cleanse as much of the colon as possible. Left lateral position to the dorsal recumbent position and then to the right lateral position during the administration so that the solution can follow the large intestine. The solution container is usually held 12 to 18 inches above the rectum because the fluid is instilled farther to clean the entire bowel. Cleansing enema (low): Cleanse the rectum and sigmoid colon. Maintains a left lateral position during administration. Carminative enema: Distends the rectum and colon with gas released from the enema solution. For an adult, 60 to 80 mL is instilled. Retention enema: Introduces oil or medication into the rectum (types): 1. Antibiotic: 2. Anthelmintic: 3. Nutritive: Types of enema:

37. Improper administration of an enema may cause electrolyte imbalance (with repeated enemas) or ruptures to the bowel or rectal tissues resulting in internal bleeding. However, these occurrences are rare in healthy, sober adults. Internal bleeding or rupture may leave the individual exposed to infections from intestinal bacteria. Blood resulting from tears in the colon may not always be visible, but can be distinguished if the feces are unusually dark or have a red hue. If intestinal rupture is suspected, medical assistance should be obtained immediately. The enema tube and solution may stimulate the vagus nerve, which may trigger an arrhythmia such as bradycardia . Enemas should not be used if there is an undiagnosed abdominal pain since the peristalsis of the bowel can cause an inflamed appendix to rupture. Recent research has shown that ozone water, which is sometimes used in enemas, can immediately cause microscopic colitis. A recent case series of 11 patients with five deaths illustrated the danger of phosphate enemas in high-risk patients. Precautions:

38. CONCLUSION