Ophthalmic Preparation Textbook PDF

Okay, here is the conversion of the provided text into a markdown format. # Ophthalmic Preparation Ophthalmic preparation Dr. Alzomor Ophthalmic Preparation: are sterile pharmaceutical preparation, free from foreign particles, and specially prepared for installation in the eye. Dr. Alzomor ##...

Okay, here is the conversion of the provided text into a markdown format. # Ophthalmic Preparation Ophthalmic preparation Dr. Alzomor Ophthalmic Preparation: are sterile pharmaceutical preparation, free from foreign particles, and specially prepared for installation in the eye. Dr. Alzomor ## Ophthalmic preparation use cases * **Local anesthetics**: To relief pain * **Diagnostic:** * **Mydriatic**: To dilate eye pupil and ease the examination of the eye * **Miotic**: To reduce the intra-ocular pressure associated with glaucoma * **Anti-inflammatory and Anti-infective:** to reduce inflammation to treat microbial or viral infection. ## Anatomy of the eye The most essential layer which controls the preparation of drugs into the eye is the **cornea**, while the conjunctiva is generally permeable to most drugs. Dr. Alzomor ### Eye Diagram Description The image is a detailed cross-sectional diagram of the human eye, highlighting various anatomical structures. Key components labeled include: * Conjunctiva * Ora serrata * Ciliary body * Aqueous * Iris * Anterior chamber * Cornea * Pupil * Lens * Posterior chamber * Canal of Schlemm * Vitreous * Sclera * Choroid * Retina * Macula * Artery (central retinal) * Optic nerve * Vein (central retinal) * Rectus medialis The diagram provides a clear view of how these structures are interconnected within the eye. ## The Conjunctiva It is composed of mucous glands, which secrete mucous that assists in keeping the eye moist. The conjunctiva is rich in blood vessels. If the eye is irritated by a foreign body or if there is any microbial infection, the blood vessels dilate and the eye appears red. Dr. Alzomor ## The Cornea It is the main membrane, which controls the permeation of the drugs into the eye. It is non-vascular, transparent, and rich with sensory nerves, which are essential for the sensation of pain or pressure. Dr. Alzomor ## Corneal Composition The cornea is composed of three layers: * **Epithelium layer**: A lipophilic layer composed of lipoprotein * **Stroma:** mainly aqueous in nature or hydrophilic * **Endothelium layer:** A lipoprotein layer or lipophilic Dr. Alzomor ## Transverse-Section of the eye The cornea consists of lipids, water, and lipid layers. For effective drug absorption and penetration through the cornea, biphasic solubility in water and is crucial. For example, dexamethasone (used as an anti-inflammatory agent) when formulated as dexamethasone-acetate (salt) Dr. Alzomor Also, if it is formulated as dexamethasone-sodium phosphate, it will have low lipid solubility and high water solubility, resulting in poor absorption; therefore, biphasic solubility is important. Most drugs used in ophthalmic preparations are weak basic drugs of acidic salts such as Pilocarpine-Hcl or Atropin-So4 (why)? Dr. Alzomor ## Lachrymal fluid/Tears It is a physiological fluid secreted by lachrymal glands, which are located at the corners of the upper lid. The excess fluid or tears is usually drained into the nasal cavity. Lachrymal fluid have a PH of 7.4 and lysozyme (which contains electrolytes such as sodium chloride and sodium bicarbonate as well as proteins). Dr. Alzomor ## Function of Lachrymal Fluid * It contains lysozyme, which has antibacterial action to protect the eye against microbial contamination. * It is secreted to protect the eye and keep it moist. * It dilutes or washes off any irritant substances from the cornea, so it acts as a buffer to neutralize any irritant effect. * The eye can hold a maximum volume of 30 µl (micro liters) and any excess volume will be drained. Dr. Alzomor ## Formulations of Ophthalmic Preparation Drugs are formulated as ophthalmic preparations in the form of: * Solutions * Suspensions * Ointments * Ocuserts (Ophthalmic Inserts) ## Ophthalmic Solutions Ophthalmic solutions are classified into: 1. Oil Solutions 2. Aqueous Solutions Dr. Alzomor ### Oil Ophthalmic Solution It is a sterile solution in which the drug is totally dissolved in oil vehicles (usually castor oil) and is intended for instillation into the eye. In these solutions, no preservatives or buffers or smoking agents are included in the formulation, because oily solutions do not support the growth of micro-organisms, and there is no change in PH and they have high viscosity-no smoking agent is needed. Dr. Alzomor An example of ophthalmic oily solution is that of pilocarpine in castor oil (used to treat glaucoma). As the oil formulation is highly viscous, it will remain in contact with the conjunctiva for a prolonged period of time and it will enhance the absorption of the drug and will give a prolonged duration of action, but it may interfere with eye vision, resulting in hazy or blurred vision. Dr. Alzomor ### Aqueous ophthalmic solution It is a sterile solution of drugs and other suitable ingredients dissolved in aqueous vehicles and are intended for instillation into the eye. Most drugs are prepared as aqueous ophthalmic solutions. Dr. Alzomor When preparing aqueous ophthalmic solutions, the following processes or treatments should be observed: * Sterility and preservation (The preparation should be sterile and preserved). * Isotonicity (The preparation should be isotonic with lachrymal fluid). * Buffering (Should be suitably buffered). * Thickening agents (or viscosity increasing agents), these are sometimes added to aqueous solutions. Dr. Alzomor ## Sterilization of ophthalmic solutions can be achieved by one of the following methods: 1. Autoclaving 2. Filtration Dr. Alzomor ## Preservation of solution To prevent the growth of microorganisms or to destroy them during the course of use of the preparation, an antimicrobial agent or preservative is added to ophthalmic solutions. Dr. Alzomor ## Properties of preservatives used The preservative used should be: * Non-irritant, Non-toxic & inert * Effective against a wide range of microorganisms, especially Pseudomonas aeruginosa * Compatible with other ingredients * Soluble & Stable in the buffer solution used * Stable & withstand high temperatures applied in the sterilization by autoclaving Dr. Alzomor ## Examples of commonly used preservatives: - Phenyl mercuric nitrate (PMN) - Benzalkonium chloride - Chlorobutanol Dr. Alzomor ## Isotonicity An isotonic or an iso-osmotic solution is a solution which has an equal osmotic pressure to that of the body fluids, including blood and lachrymal fluid. The solutions which have lower osmotic pressure than body fluids are referred to as hypotonic, while the solutions that have higher osmotic pressure than body fluids are referred to as hypertonic solutions. ## Method of calculating isotonicity for ophthalmic solutions: * Sodium chloride equivalent method * Freezing point depression method Dr. Alzomor ## How to maintain the solubility and stability of the drug? **(I) To maintain solubility:** Generally, buffers having low pH (4-5) are suitable for: the solubility of basic drugs such as: * Local anesthetics: e.g. Procaine, Dibucaine(as Hcl salts). * Pilocarpine Hcl (miotic to treat glaucoma). * Atropine So4 (mydritic to assist eye examination). Boric acid buffer can provide pH of(4-5) (by dissolving 1.9g of boric acid in 100 ml of water). Dr. Alzomor While buffers having a high pH (6-8) are suitable for the solubility of acidic or neutral drugs such as: * Sulphacetamide sodium (antibiotic) - acidic drug * Flurbiprofen sodium (anti-inflammatory) - acidic drug * Prednisolone acetate (anti-inflammatory) - neutral drug Phosphate buffer provides a pH range of (6-8), prepared by mixing a sodium dihydrogen phosphate and disodium hydrogen phosphate in different proportions to produce the required pH. Dr. Alzomor ## (ii) To maintain stability: The pH chosen or the buffer chosen should provide a stable environment for the drug. Generally drugs, such as Pilocarpine or Procaine, are degraded at a low pH and at a high PH. So for such drugs, a PH maximum stability should be chosen to avoid their degradation. Dr. Alzomor ## Thickening agents In some ophthalmic solutions, suitable thickening agents are used or added to maintain the viscosity of the solution and therefore assist in holding the drug in contact with the eye tissues so as to enhance its absorption hence its effectiveness. **Examples of thickening agents** * Cellulose derivatives such as * Methyl cellulose * Hydroxyl propyl cellulose * Hydroxyethyl cellulose * 2-Polyvinyl alcohol * 3- polyvinylpyrrolidone Dr. Alzomor ## II-Ophthalmic suspension: Ophthalmic suspensions are sterile preparations in which the insoluble drugs products are suspended or dispensed in an aqueous vehicle, and the also contains additives such as suspending agents, tonicity adjusting substances, buffering agents, and preservatives. Dr. Alzomor ## Why we Prepare Ophthalmic Suspension? If the drugs are unstable and hydrolysable and if prolonged action is required. Properties of the ideal ophthalmic suspension: * It should be sterile and well-preserved. * It should be dispersed easily and give a uniform dose and have good distribution properties. * It should be isotonic using a suitable buffer to minimize the irritation. Dr. Alzomor ## Example of the ophthalmic suspension: * Tetracycline ophthalmic suspension * Oxytetracycline and hydrocortisone ophthalmic suspension * Sulphacetamide and prednisolone ophthalmic suspension Dr. Alzomor ## III- Ophthalmic Ointment Ophthalmic ointment is a sterile semi-solid preparation. Ophthalmic ointment contains drugs, which incorporated into the ointment bases. A ribbon of the ointment is applied to the lower eyelid without touching the eye by pulling down the lower eyelid. Dr. Alzomor ## Preparation of the Ointment The ointment base was melted and the fine powdered drug was added and triturated well until homogenization. The mixture is sterilized by using dry heat sterilization method (the mixture is placed in the sterilization equipment (oven) for two hours and at 170°C). Then, the sterilized ointment is filled into a collapsible plastic tube previously sterilized. The tubes are closed with screw caps made of aluminum or plastic. Dr. Alzomor ### Ointment Bases Hydrocarbon bases, which consist of: * Yellow soft paraffin * Liquid paraffin * Anhydrous lanolin. ### Properties of Ointment Bases * Inert, non-irritant, and non-toxic * Compatible with drugs incorporated * It releases the drug after melted at body temperature. * Thermo-stable at high temperature Dr. Alzomor ## Advantages of Ophthalmic Ointments Due to the viscosity of the base and long contact with the tissues this lead to: 1- Slow release of the drug 2- Prolong action of the drug ## Disadvantages of Ophthalmic Ointments It produces a hazy vision as a result of an oily film formed over the conjunctiva. **Example of the ophthalmic ointments** * Atropine sulphate * Chloramphenicol * Neomycin Dr. Alzomor ## IV-(Ocuserts) Ophthalmic Inserts A newly developed device for the insertion of the drug to the lower eye lid. They are of design which provide a constant and continuous drug release for a longer period of time. Ocusert are transparent, sterile oval in shape. Dr. Alzomor Ocuserts composed of reservoir containing the medicaments and they are surrounded in each side polymeric membrane. *Polymeric membrane* controls the rate of the release of the drug from the reservoirs. Such *polymeric membrane* is composed of very thin microscopic holes that control the release of the drug. **Example of the ocuserts** Pilocarpine, such ocuserts release the drug at a constant rate of 20-40-80 ug/hr for 7 days. Dr. Alzomor ## Advantages of Ocuserts * It is more convenient than other Ophthalmic preparation * Sense it is used for long period of time * It gives continuous drug release * It is used for chronic disease such as glaucoma. Dr. Alzomor ## Ophthalmic Drugs Used in Control Eye Disease * Antiseptics: Silver and ammonium nitrate * Antibiotics: Gentamicin, Neomicin, Chloramphenicol, Tetracyclin and Sulphcetamide. * Anti-inflammatory: Hydrocortisone, prednisolone and Dexamethasone * Local anesthetics: Procaine, Tetracaine, Dibucaine and proparacain. * Miotics: Pilocarpine (reduce the pressure associated with glaucoma) * Myrdrotics: Atropine, Scopolamine (dilate the eye pupil in case of the eye examination * Diagnostics: Fluorescin is used in the detection of the corneal ulceration. * Beta Adrenergic blocking agents = Anti-adrenergic: Timolol and Betaxolo (they reduce the intra-ocular pressure associated with glaucoma) * Anti-allergic: Sodium chromoglycate * Vasoconstriction: Naphazolin, Phenyleherine and Tetrahydrozoline Dr. Alzomor # Pharmaceutical Aerosols ## Pharmaceutical Aerosols **Definition:** A suspension of small solid particles or droplets suspended in a gas or vapor. **Pharmaceutical aerosols** are usually unstable. **Common perception:** Products that depend on the pressure of a compressed or liquefied gas to expel the contents from a container. ### Aerosol Can Diagram description The image shows a diagram of an aerosol canister labeled with the following attributes: 1. Actuator 2. Aerosol 3. Valve stem 4. Valve 5. Compressed gass 6. Propellant vapor 7. Canister anatomy 8. Dip tube 9. Liquified propellant or solvent Dr. Alzomor ## Uses of Pharmaceutical Aerosols | Topical | Advantages | | :------------------------------------ | :--------------------------------------------------------------- | | Local anesthetics (e.g., Benzocaine) | Convenient | | Wound washing | No need to touch skin | | Rubefacients (e.g., Methylsalicylate) | Minimal contamination of the unused product. | | Proprietary burn applications | | | Antibacterials (e.g. Neomycin) | | | Antifungal sprays (Miconazole) | | | Anti-inflammatory steroids | | | (e.g., Dexamethasone) | | Dr. Alzomor | Oral and Lingual | | :----------------------------------------------------------- | | Antacids (e.g. Aluminum and magnesium silicate) | | Local anesthetics (e.g. Lidocaine) | | Antiseptics (e.g. Chloroseptic) | | Anti-anginals (e.g. Nitroglycerin) | Dr. Alzomor | Vaginal | Advantages | | :------------------------------ | :---------------------------------------------------------------------------------------------------------- | | Contraceptive Foams (e.g. Nonoxynol-9) | 1. Provides access to hard-to-reach sites 2. Expands to fill available space and provide complete surface coverage | | Rectal | | Local anesthetics (e.g. Pramoxine) | | Anti-inflammatory steroids (e.g. Hydrocortisone) | | | Dr. Alzomor | Respiratory | | :-------------------------------------------- | | Bronchodilators (e.g. Albuterol) | | Anti-inflammatory steroids (e.g. Beclomethasone) | | Anti-allergics (e.g. Cromolyn sodium) | | Antivirals (e.g. Ribavirin) | | Smoking cessation (e.g. Nicotine) | | Migraine (e.g. Ergotamine tartrate) | Dr. Alzomor | Nasal | Advantages | | :----------------------------------------- | :-------------------------------------------------------------------------------------------------------- | | Decongestants (e.g. Phenylephrine) | 1. Provides access to hard-to-reach sites 2. minimal dripping (soaked) | | Anti-inflammatory steroids (e.g. Beclomethasone) | | Anti-allergics (e.g. Cromolyn sodium) | | | Moisturizers (e.g. Normal saline) | | | Systemic access | | - Antidiuretics (e.g. Desmopressin) | | | - Antismoking (Nicotine) | | | Ocular | Dr. Alzomor | | Contact lens cleaning solutions (not applied directly to the eye) | | Dr. Alzomor ## Advantages of Pressurized Delivery Systems * Easy to use and convenient * The remaining product is not contaminated during use. Aerosols can be filled aseptically. * Tamper-proof * Protect unstable drugs from light, oxygen, and water * The target site need not be touched; this is especially important in burns. Dr. Alzomor ## Disadvantages of Pressurized Delivery Systems * Expensive * Performance can deteriorate during the life of the product * Limited safety hazard *Flmable * Pressurized *Inadvertent inhalation * Sometimes, the product can be used incorrectly * Most topical and nasal sprays are now converted to water-based pump sprays Dr. Alzomor ## Aerosol Formulation | | Components | | :---------------------- | :----------------------------------------------------------------------------- | | 1. | Active ingredient (drug) | | 2. | Solvents / co-solvents | | 3. | Propellant system | | 4. | Surfactants | | 5. | Miscellaneous | | | 1. Antioxidants 2. Preservatives 3. Flavoring agents 4. Buffers. 5. Perfumes | Collectively, the drug and less volatile components are termed the "slurry" or "concentrate." Dr. Alzomor ## Formulation of Pressurized Aerosol Systems * Propellants provide the driving force to expel the product from its container * Provide dispersion medium ## Formulation of Pressurized Aerosol Systems | Types of Pressurized Formulation | | | :------------------------------- | :------------------- | | Two Phase System | Three Phase Systems | | Dry mist | Wet mist | | Liquefied Propellant | Propellant Vapor | | Wet mist | Form | | Solvent | : | Dr. Alzomor ## Propellants **1- HYDROCARBON Propellants (most common)** | Advantages | Disadvantages | | :--------------------------- | :---------------------------------------- | | Inexpensive | Flammable | | Minimal ozone Depletion | Aftertaste | | Excellent solvents | Unknown toxicity following inhalation | | | Low liquid density Pressurized Aerosol Formulations | Dr. Alzomor ## HYDROCARBON Propellants (most common) | Property | n-Butane | Isobutane | | | :--------------------------------- | :----------------------- | :------------------------- | | Formula | | | $CH(CH_3)_3$| | Flammability limits in air (%w/v) | 1.9 - 8.8 | 1.8 - 8.4 | | Boiling point (oC) | -0.5 | -11.7 | | Vapor pressure at 25oC (Pounds/square inch) | 31 | 45 | | Liquid density at 25oC (g/ml) | 0.58 | 0.56 | Dr. Alzomor ## **2-CHLOROFLUORCARBONS (Used only in Inhalation Aerosols)** | Advantages | Disadvantages | | :------------------------- | :----------------------------------------- | | Low inhalation toxicity | Destructive to atmospheric Ozone | | Hight chemical stability | High cost | | High purity | | | CFC-11 is a good solvent | | Dr. Alzomor | | CFC - Physical Properties | | | :---------------------------- | :--------------------------------------------------------------------- | :------- | | Property | CFC-11 | CFC-12 | | Formula | CPCF| | | Flammability limits in air (% w/v) | None | None | | Boiling point (oC) | 23.8 |15.3 | | Vapor pressure at 25oC (Pounds/square inch) | none | | Liquid Density at 25oC (g/ml) | 1.48 | 1.31 | ## 3-HYDROFLUOROALKANES (aka hydrofluorocarbons) | Advantages | Disadvantages | | :-------------------------- | :------------------- | | Low inhalation toxicity | Poor solvents | | High chemical stability | High cost | | High purity | | | Not zone Depleting | Dr. Alzomor | [1,1,1,2,3,3,3 - Heptafluoropropane (HFA-227) 1,1,1,2 - Tetrafluoroethane (HFA-134a)] ## 3- COMPRESSED GAS PROPELLANTS | Advantages | Disadvantages | | :----------------------------- | :---------------------------------- | | Low inhalation toxicity | Requires the use of a nonvolatile co-solvent | | High chemical stability | Produce course droplet sprays | | High purity | Pressure falls during use | | Inexpensive |Dr. Alzomor | Dr. Alzomor |Property| Carbon Dioxide| Nitrous Oxide| | --- | --- | --- | | Formaula | CO2 | $N_2O$| |Flammability limits in air (%w/w)|None|None| |Boiling point °C|-78.3|-195.6| |Vapor Pressure|Depend on fil|Depends on fill| |Liquid density|Not a liguid |Not a liquid Dr. Alzomor ## Types and Function of Surfactants | * Anionic, e.g. and oleic acid. * Cationic, e.g. cetylpyridinium chloride * Zwitterionic, e.g. phosphatidylcholine. * Nonionic e.g. sorbitan trioleate Dr Alzomor ## Types & Function of Surfactants . **Function of Surfactants** Valve & lubrication Aid hormogenous the dispertion of salid. particle in solvant & prpeel lant system Maintain of stability of t foaming aerosol Emulsily propellant and aqueous phase in emulsion aerosol. Enhance dissolution of medication propellant os solvant Sustem Dr. Alzomor. ## Formulation of the drug (*Active ingredient*) Drug may be dissolved in the propellant system, * Smaller Spray particle size can be achieved after complete Propel laint evaporation * Simplified Manufacturing Process. Drug must be soluble. Chemical degradation may occur faster Dr. Alzomor ## Formulation of drag (active ingredient) The drug can be **suspented** in the (* propellent system*) • Can be used to diver insoluble drus - • Higher doses can be delivered, Constants agitation during manufacturing as we required * Physical instabiliz must be and a problems Dr. Alzomor. Selection of drug particle size The size of a suspended drug particles depends on the *intended use of the product* * Less than **5MICron** for inhalation aerosols, (Sometimes caHed" Micromized" "paticiel" 10/40 microns for topical sprays ( >50 microns feel *gritty" Skiny") DR. Alzomor. ## COSolsant Solvents / cosolVents are less volatile than the propellants - They may be used to * dissolve medicine in a propellant |Solvent System. Lower the Vapor Pressure of the *Propellant System** * promote a miscibility between propellant s asnd emulsi ble Sotvents " Solvents increase the droplet Size ad Weatness Water' - Alcohols for a. g, Ethanol and and the isopropanol DR. Alzomor.. ## There is something here ## Example Composition Description of Table with the attributes: * Ingrediant * Acrive * Sufacantant * Propellant * (CO) *Soent * Misc. Excipients and type as ouput". ### List of DR- Alzomor.. * Types Pressurized Aerosol formulation. * 1 **sprays** Fine dry Spays. *(Inhalastion aerosois "Coarse dry sprays :Artifungal" -**Deodorants-s** *Coarse wets"Spray (WM/Q (Emulsion) Antisethic sprays **(2- Foume" Stuble foams (olw (imolsions,). ***Ratell antia infiammalsony foum # *Packaging compunents*. ### A - plastic coated glass Allow the lovel catent. To Be Seen compatilole with the most Formulations, plastic Coating Absords" "neckshock"during crimping and provides. Bamer to brokern ylass Poor to the aesthetic Visual Finsh , difficult to Label heavy . + Used from inhalations aerosol Conteining disspited frug. *DR ALzomor **BAluminium** - Lightweght and sealess -Can Be Screen Printed, there fore visually appealing (atrractive *Easy to fill and crimp. "Incompatiole with some propellant and colyenta Can be epoxy caated. Opaque "Used" for imalaton and topical aerosols. DR. Alzomor ## Valves * A-Continuous (used for most topical aerosols) * Product IS released as long as pressure IS maintained on the actuator. B- Metered (Used For all inhalation, & some topical aerosols) * A definite volume of product IS released wh en the actuator IS pressed. No nrore product is released Unless the actuator IS returned to iits rest position and repressed - zx-isout for inhaiation aerosols up to s ml Tor topical acrosois ### Dargam Desoribe The an image is meter of that components. The parts from a ferrule to gasket * Valve closed(mormai Positon) * Valve o Pen the aclvaled the pasition. * Pulonary drag deivery. The image desoribis the Pulmonary the deliery The operation s : are coid filhng and preuss the filling.. Dr. Alzomor 140