it is a complete overview on ophthalmic dosage form. beginning from anatomy and physiology of eye with drug absorption mechanism including all factors to formulation considerations and evaluation of the products i.e. eye drops and eye ointment & the evaluation tests. it will help you make the concepts clear about ophthalmic drug deliveries.
it is a complete overview on ophthalmic dosage form. beginning from anatomy and physiology of eye with drug absorption mechanism including all factors to formulation considerations and evaluation of the products i.e. eye drops and eye ointment & the evaluation tests. it will help you make the concepts clear about ophthalmic drug deliveries.
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
Short review about parenteral suspension, principle consideration during formulation, factors affecting formulation etc. are included in this presentation.
Pharmaceutical aerosols have been playing a crucial role in the health and wellbeing of millions of people throughout the world for many years. These products include pressurized metered dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, sublingual’s, skin sprays (coolants, anaesthetics, etc.) and dental sprays. The technology’s continual advancement, the ease of use, and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years.
Many of the tests required for the evaluation of MDIs are similar to those used for other dosage forms. These include description, identification, and assay of the active ingredient; microbial limits; moisture content; net weight, degradation products and impurities (if any); extractable; and any other tests deemed appropriate for the active ingredient.
Bio pharmaceutical classification System [BCS]Sagar Savale
The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues.
Definition:
“The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate”.
To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System
Introduction
Routes of administration of parenteral dosage form
Types of parenteral preparation
General requirements for parenteral dosage form
Formulation of parenteral preparations
Containers and closures used
Processing of parenteral preparations
Evaluation of parenteral preparations
Labeling and packaging
Production facilities
Preparation of iv fluids and admixtures
Sterlity testing
Particulate matter monitoring
Faculty seal packaging
Introduction to ophthalmic products useful as a basic & theoretical tool for pharmacy, medical & nursing students for their graduate and post graduate studies
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
Short review about parenteral suspension, principle consideration during formulation, factors affecting formulation etc. are included in this presentation.
Pharmaceutical aerosols have been playing a crucial role in the health and wellbeing of millions of people throughout the world for many years. These products include pressurized metered dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, sublingual’s, skin sprays (coolants, anaesthetics, etc.) and dental sprays. The technology’s continual advancement, the ease of use, and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years.
Many of the tests required for the evaluation of MDIs are similar to those used for other dosage forms. These include description, identification, and assay of the active ingredient; microbial limits; moisture content; net weight, degradation products and impurities (if any); extractable; and any other tests deemed appropriate for the active ingredient.
Bio pharmaceutical classification System [BCS]Sagar Savale
The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues.
Definition:
“The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate”.
To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System
Introduction
Routes of administration of parenteral dosage form
Types of parenteral preparation
General requirements for parenteral dosage form
Formulation of parenteral preparations
Containers and closures used
Processing of parenteral preparations
Evaluation of parenteral preparations
Labeling and packaging
Production facilities
Preparation of iv fluids and admixtures
Sterlity testing
Particulate matter monitoring
Faculty seal packaging
Introduction to ophthalmic products useful as a basic & theoretical tool for pharmacy, medical & nursing students for their graduate and post graduate studies
the all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Anatomy of eye and adrena, absorption of drug in the eye, classification of ophthalmic
products, safety consideration of ophthalmic products, formulation, vehicles and additives,
manufacturing consideration, environment, manufacturing techniques, quality control of
ophthalmic products, packaging of ophthalmic products.
Ophthalmic dosage are the preparation designed for application to the eye:-
For treatment
For symptomatic release of symptoms
For diagnostic purpose
As aid to surgical procedures
They are the sterile products meant to instillation in to the eye in the space between eye lid and the eye ball
They are also prepared as parenteral product. Example
Eye drops, Eye lotion, Eye ointment, Eye suspension, Contact lens solution
Introduction
Rheology and Viscosity
Rheology in Pharmaceuticals
• Pharmaceutical formulation
• Pharmaceutical manufacturing
• Dispensing pharmacy
• Pharmaceutical technology
• Physical pharmacy
• Pharmaceutical jurisprudence
Scope of rheology
Applications:
Examples
Conclusion
Rheology has applications in materials science engineering, geophysics, physiology, human biology and pharmaceutics. Materials science is utilized in the production of many industrially important substances, such as cement, paint, and chocolate, which have complex flow characteristics. In addition, plasticity theory has been similarly important for the design of metal forming processes. The science of rheology and the characterization of viscoelastic properties in the production and use of polymeric materials has been critical for the production of many products for use in both the industrial and military sectors. Study of flow properties of liquids is important for pharmacists working in the manufacture of several dosage forms, such as simple liquids, ointments, creams, pastes etc. The flow behavior of liquids under applied stress is of great relevance in the field of pharmacy. Flow properties are used as important quality control tools to maintain the superiority of the product and reduce batch to batch variations
• Acid-base concept
• Role of this form of titration in pharmaceutical quality assurance
• Ionization
• Low of ionization
• Henderson hasselbarkh equation equation
• Neutralization curves
• Acid-base indicators
• Mixed indicators used in polyprotic & amino acid systems during amino acid titration
• Introduction
• The main activities of community pharmacists
• Processing of prescriptions
• Care of patients or clinical pharmacy
• Extemporaneous preparation and small-scale manufacture of medicines
• Traditional and alternative medicines
• Monitoring of drug utilization
• Responding to symptoms of minor ailments
• Informing health care professionals and the public
• Health promotion
• Domiciliary services
• Rational Use of Drugs
• Individualization of Drug
• Community Pharmacists Play Key Role in Improving Medication Safety
• Pharmacists as a Community Resource
• Conclusion
Definition
History
role of biotransformation
where drug biotransformation occur
the pathway of drug metabolism
phase 2 reaction
plasma level time curve of mephenytoin
factors affecting drug metabolism
importance of biotransformation
Impact of pharmacokinetics of bextrum gold and tetracycline from drug drug in...Md. Mynul Hasan
Definition
tetracycline
absorption of tetracycline and bextram gold
Drug-drug interaction
pharmacokinetics of bextram gold tetracycline
adsorption
result
definition
type
Biological hazards
fire and explosion hazards
preventive measures
safety measures
gas hazards
gas safety at work
mechanical hazards
dust hazards
industrial pollution
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. 1
OPHTHALMIC PRODUCTS
Definition: They are specialized dosage forms designed to be instilled onto the external surface of the eye
(topical), administered inside (intraocular) or adjacent (periocular) to the eye or used in conjunction with an
ophthalmic device.
The most commonly employed ophthalmic dosage forms are solutions, suspensions, and ointments.
These preparations when instilled into the eye are rapidly drained away from the ocular cavity due to tear flow
and lacrimal nasal drainage.
The newest dosage forms for ophthalmic drug delivery are: Gels, Gel-forming solutions, Ocular inserts ,
Intravitreal injections and Implants.
Drugs Used in The Eye:
• Miotics e.g. pilocarpine Hcl
• Mydriatics e.g. Atropine
• Cycloplegics e.g. Atropine
• Anti-inflammatories e.g. corticosteroids
• Anti-infectives(antibiotics, antivirals and antibacterials)
• Anti-glucoma drugs e.g. pilocarpine Hcl
• Adjuncts e.g. Irrigating solutions
• Diagnostic drugs e.g. sodiumfluorescein
• Anesthetics e.g. Tetracaine
Ideal Requirements:
Following characteristics are required to optimize ocular drug delivery system:
• Good corneal penetration.
• Prolong contact time with corneal tissue.
• Simplicity of instillation for the patient.
• Non irritative and comfortable form
• Appropriate rheological properties
• Sterility, clarity, buffer, buffer capacity and pH, tonicity, viscosity, stability, comfort, additives,
particle size, packaging and preservatives
• The buffer system must be considered with tonicity and comfort in mind.
• Stability can be related with pH, buffer and packaging.
• Sterilization important in terms of stability and packaging.
• Solutions must be free from foreign particles.
• Solutions pH must be optimum.
• More than one sterilization methods are employed.
• Sterile solutions, suspension and ointments usually contain antimicrobial preservatives.
3. 2
EYE ANATOMY:
Cornea: clear front window of the eye that transmits and focuses light into the eye.
Iris: colored part of the eye that helps regulate the amount of light that enters
Pupil: dark aperture in the iris that determines how much light is let into the eye
Lens: transparent structure inside the eye that focuses light rays onto the retina
Retina: nerve layer that lines the back of the eye, senses light, and creates electrical impulses that travel
through the optic nerve to the brain
4. 3
Macula: small central area in the retina that contains special light-sensitive cells and allows us to see fine
details clearly
Optic nerve: connects the eye to the brain and carries the electrical impulses formed by the retina to the
visual cortex of the brain
Vitreous: clear, jelly-like substance that fills the middle of the eye
DOSAGE FORMS APPLIED TO THE EYE:
Topical Administration Solutions
Suspension
Emulsion
Ointment
Gel
Perfusion
Spray
Inserts
Intraocular drug delivery
Intraocular injection
Implant Iontophoresis
Liposome
Niosome
Bioavailability:
• Under normal conditions human tear volume averages about 7µL.
• The estimated maximum volume of cul-de-sac is about 30µL.
• Many commercial eyedrops range from 50-75µL in volume to minimize drainage loss.
Corneal Absorption:
1. Drugs administered by instillation must penetrate the eye & do so primarily through the cornea.
2. Corneal absorption is much more effective than scleral and conjuctivital absorption.
3. Many ophthalmic drugs are weak bases and are applied into eye as aqueous solutions of their salts. 4.
Depending upon pH, drug gets dissociated and pass through cornea, iris and ciliary body to the site of its
pharmacological action.
5. Since, cornea is a membrane including both hydrophilic and lipophilic layers.
6. Most effective penetration is obtained with drugs having both lipid and hydrophilic properties.
6. 5
Classification of Ophthalmic Products:
General Safety Considerations:
1. Sterility
2. Ocular Toxicity & Irritation
3. Preservation & Preservatives
Sterility
1. A sterile suspension, bottle, caps, dropper tips may be sterilized by using ethylene oxide or gamma radiation;
2. A suspended solid may be sterilized by dry heat, gamma radiation, or ethylene oxide;
3. A aqueous portion of composition may be sterilized by filtration;
4. A compounding is completed under aseptic conditions.
• Solutions
• Suspensions
• Powders for
• reconstitution
• Sol to gel systems
Liquid
• Ocular insertsSolid
• Ointments
• Gels
Semi-
Solid
• Injection
• implants
• irrigating solution
intraocular
7. 6
5. This sterile manufacturing process must then be validated to prove that NMT 3 containers in a lot of 3000
containers (0.1%) are non-sterile.
2. Ocular Toxicity & Irritation
1. Albino rabbits are used to test the ocular toxicity and irritation of ophthalmic formulations.
2. The procedure based on the examination of the conjunctiva, the cornea or the iris.
3. E.g. USP procedure for plastic containers:
1. Containers are cleaned and sterilized as in the final packaged product.
2. Extracted by submersion in saline and cottonseed oil.
3. Topical ocular instillation of the extracts and blanks in rabbits is completed and ocular changes examined.
4. A modified ‘Draize test’: official method for evaluation of acute ocular irritancy in rabbits.
3. Preservation & Preservatives
1. Preservatives are included in multiple-dose eye solutions for maintaining the product sterility during use.
2. Preservatives not included in unit-dose package.
3. The use of preservatives is prohibited in ophthalmic products that are used at the of eye surgery because, if
sufficient concentration of the preservative is contacted with the corneal endothelium, the cells can become
damaged causing clouding of the cornea and possible loss of vision.
4. So these products should be packaged in sterile, unit-of-use containers.
5. The most common organism is Pseudomonas aeruginosa that grow in the cornea and cause loss of vision.
6. Staphylococcus aureus is responsible for most bacterial infections of the eye.
Examples of Preservatives:
1- Cationic Wetting Agents:
• Benzalkonium chloride (0.01%):
• It is a quaternary ammonium compound and most widely used preservative.
• It is generally used in combination with 0.01-0.1% disodium edetate (EDTA). The chelating, EDTA has the
ability to render the resistant strains of P. aeruginosa more sensitive to benzalkonium chloride.
8. 7
2- Organic Mercurials:
• When Benzalkonium chloride could not be used in a particular formulation, one of the following organic
mercurial'sis used:
• Phenyl mercuric nitrate: 0.002-0.004%
• Phenyl mercuric acetate: 0.005-0.02%.
• Thimerosal: 0.01-0.02%
3- Alcohol Substitutes:
• Chlorobutanol(0.5%). Effective only at pH 5-6.
• Phenyl ethanol (0.5%)
5. Methyl & Propyl Paraben:
• They are used in combination, with methyl paraben (0.03-0.1%) and propyl paraben (0.01-0.02%)
• Parabens have also been shown to promote corneal absorption.
6. Cetrimonium Chloride:
• Used in dry eye treatment (0.01%)
Sterilization:
1. Moist heat sterilization
2. Membrane filtration
3. Gaseous sterilization
4. Radiation sterilization (60Co)
Artificial Tears:
• Artificial tears are lubricant eye drops used to treat the dryness and irritation associated with deficient tear
production in Keratoconjunctivitis Sicca (dry eyes).
• They are also used to moisten contact lenses and in eye examinations.
• Artificial tears are available over-the-counter.
• Artificial tears are supplemented with other treatments in moderate to severe forms of dry eyes.
9. 8
• Application of artificial tears every few hours can provide temporary relief from the symptoms of dry eyes.
• Hydroxypropylcellulose stabilizes and thickens the precorneal tear film and prolongsthe tear film breakup
time. 25
Composition of Tears:
• Preparations contain Carboxymethylcellulose, Polyvinyl alcohol, Hydroxypropyl methylcellulose (a.k.a. HPMC
or hypromellose), Hydroxypropylcellulose and Hyaluronic acid (a.k.a. Hyaluronan, HA).
• They contain water, salts and polymers but lack the proteins found in natural tears.
• Patients who use them more frequently than once every three hours should choose a brand without preservatives
or one with non-irritating preservatives.
• Besides lubricating your eyes, some artificial tears contain electrolytes.
• These additives may promote healing of the surface of the eyes.
• Artificial tears may also contain thickening agents, which keep the solution on the surface of your eyes longer.
Additives:
• The inactive ingredients in ophthalmic solution and suspension dosage forms are necessary to perform one or
more of the following functions:
• Adjust concentration and tonicity
1. Buffer and adjust pH,
2. Stabilize the active ingredients against decomposition ,
3. Increase solubility,
4. Impart viscosity
5. Act as solvent.
1- Tonicity and Tonicity-Adjusting Agents:
1. The pharmacist should adjust the tonicity of an ophthalmic correctly (i.e. exert an osmotic pressure equal to
that of tear fluid, generally agreed to be equal to 0.9% NaCl ).
2. A range of 0.5-2.0% NaCl equivalency does not cause a marked pain response and a range of about 0.7-1.5%
should be acceptable to most person.
10. 9
3. Commonly tonicity adjusting ingredients include: NaCl, KCL, Buffer salts, Dextrose, Glycerin, Propylene
Glycol, Mannitol.
Isotonicity:
Lacrimal fluid is isotonic with blood having an isotonicity value corresponding to that of 0.9% NaCl solution
2- pH Adjustment and Buffers:
pH adjustment is very important as pH affects
1- To render the formulation more stable
2- The comfort, safety and activity of the product. Eye irritation Increase in tear fluid secretion Rapid loss of
medication.
3- To enhance aqueous solubility of the drug.
4- To enhance the drug bioavailability 5- To maximize preservative efficacy
• Ideally, every product would be buffered to a pH of 7.4 (the normal physiological pH of tear fluid ).
• When necessary they are buffered adequately to maintain stability within this range for at least 2 years.
• If buffers are required there capacity is controlled to be as low as possible( low buffer capacity) thus enabling
the tear to bring the pH of the eye back to the physiological range .
3- Stabilizers & Antioxidants:
• Stabilizers are ingredients added to a formula to decrease the rate of decomposition of the active ingredients.
• Antioxidants are the principle stabilizers added to some ophthalmic solutions, primarily those containing
epinephrine and other oxidizable drugs.
• Sodium bisulfite or metabisulfite are used in concentration up to 0.3% in epinephrine hydrochloride and
bitartrate solutions.
• The several antioxidant system have been developed: These consists of ascorbic acid and acetylcysteine and
sodium thiosulfate .
4- Surfactants:
• The order of surfactant toxicity is : Anionic > Cationic >> Non-ionic
• Several nonionic surfactants are used in relatively low concentration to aid in dispersing steroids in
suspensions and to achieve or to improve solution clarity.
• Those principally used are the sorbitan ether esters of oleic acid ( Polysorbate or Tween 20 and 80 ).
11. 10
5- Viscosity-Imparting Agents:
• Polyvinyl Alcohol, Methylcellulose, Hydroxypropyl Methylcellulose, Hydroxyethylcellulose, and Carbomers,
are commonly used to increase the viscosity of solution and suspensions (to retard the rate of setting of
particles)
• They increase the ocular contact time, there by decreasing the drainage rate, increase the mucoadhesiveness and
Increasing the bioavailability .
• Disadvantage: Produce blurring vision as when dry, form a dry film on the eye lids. Make filteration more
difficult.
• Commercial viscous vehicles are : 1. Polyvinyl Alcohol (liquifilm) 2. Hydroxypropyl Methylcellulose
6- Vehicles:
• Purified water meeting USP standards may be obtained by: Distillation, deionization or reverse osmosis.
• Oils have been used as vehicles for several topical eye drops products that are extremely sensitive to moisture.
• When oils are used as vehicles in ophthalmic fluids, they must be of the highest purity
Packaging:
• Plastic containers for ophthalmic preparations are made from plastic composed of a mixture of homologous
compounds having a range of molecular weights.
• Such plastics frequently contain other substances such as residues from the polymerisation process, plasticisers,
stabilisers, antioxidants, lubricants and pigments.
• The plastic bottle and dispensing tip is made of low-density polyethylene (LDPE) resin, which provides the
necessary flexibility and inertness.
• The cap is made of harder resin than the bottle.
• A special plastic ophthalmic package made of polypropylene is introduced. The bottle is filled then sterilized
by steam under pressure at 121°C.
• For deciding the suitability of a plastic for use as a container for ophthalmic preparations, factors such as the
composition of the plastic, processing and cleaning procedures, contacting media, adhesives, adsorption and
permeability of preservatives, conditions of storage, etc. should be evaluated by appropriate additional specific
tests.
• Plastic containers for ophthalmic preparations comply with the following tests.
– Leakage test;
– Collapsibility test;
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– Clarity of aqueous extract;
– Non-volatile residue and
– Eye irritation tests.
• Powder for reconstitution also use glass containers, owing to their heat-transfer characteristics, which are
necessary during the freeze-drying processes.
• The glass bottle is made sterile by dry-heat or steam autoclave sterilization.
• Amber glass is used for light-resistance.
Isotonicity:
1. Solutions containing the same concentration of particles and thus exerting equal osmotic pressures are called
isoosmotic.
2. A 0.9% solution of NaCl (Normal Saline) is iso-osmotic with blood and tears.
3. The term isotonic, meaning equal tone, is sometimes used interchangeably with the term iso-osmotic.
4. The clinical significance of all this is to insure that isotonic or iso-osmotic solutions do not damage tissue or
produce pain when administered.
5. Solutions which contain fewer particles and exert a lower osmotic pressure than 0.9% saline are called
hypotonic and those exerting higher osmotic pressures are referred to as hypertonic.
6. Hypotonic solution produces painful swelling of tissues as water passes from the administration site into the
tissues or blood cells.
7. Hypertonic solutions produce shrinking of tissues as water is pulled from the biological cells in an attempt to
dilute the hypertonic solution.
8. The eye can tolerate a range of tonicities as low as 0.6% and as high as 1.8% sodium chloride solution.
9. Several methods are used to adjust isotonicity of pharmaceutical solutions:
1) Sodium chloride equivalent method
2) Freezing point depression method
3) The isotonic solution V-value method
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Evaluation of Ophthalmics:
1. Sterility Test
2. Clarity Test
3. Leaker Test
4. Metal particles in ophthalmic ointment
Sterility Test
Ophthalmic semisolids should be free from anaerobic and aerobic bacteria and fungi.
Sterility tests are therefore performed by the:
1. Membrane filtration technique .
2. Direct - inoculation techniques.
In the Membrane filtration method :
A solution of test product (1%) is prepared in isopropyl myristate and allowed to penetrate through cellulose
nitrate filter with pore size less than 0.45 μ m.
If necessary, gradual suction or pressure is applied to aid filtration.
Clarity test:
Definition: Clarity is a relative term, its mean a clear solution having a high polish conveys to the observer that the product is of
exceptional quality and purity.
Clarity test is carried out to check the particulate matter in the sample.
It is practically impossible that every unit of lot is perfectly free from visible particulate matter, that is, from
particles that are 30 to 40 micrometer and large in size.
Leakage test:
This test is mandatory for ophthalmic ointments, which evaluates the intactness of the ointment tube and its
seal.
Ten sealed containers are selected, and their exterior surfaces are cleaned.
They are horizontally placed over absorbent blotting paper .
Maintained at 60 ± 3 ° C for 8 h.
The test passes if leakage is not observed from any tube.
If leakage is observed, the test is repeated with an additional 20 tubes.
The test passes if not more than 1 tube shows leakage out of 30 tubes .
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Metal particles in ophthalmic ointment:
This test is required only for ophthalmic ointments.
The presence of metal particles will irritate the corneal or conjunctival surfaces of the eye.
It is performed using 10 ointment tubes.
The content from each tube is completely removed onto a clean 60 - mm - diameter Petri dish which possesses
a flat bottom.
The lid is closed and the product is heated at 85 ° C for 2 h.
Once the product is melted and distributed uniformly, it is cooled to room temperature.
The lid is removed after solidification. The bottom surface is then viewed through an optical microscope at
30× magnification
The viewing surface is illuminated using an external light source positioned at 45 ° on the top.
The entire bottom surface of the ointment is examined, And the number of particles 50 μm or above are
counted using a calibrated eyepiece micrometer.
The USP recommends that the number of such particles in 10 tubes should not exceed 50, with not more than
8 particles in any individual tube.
limits are not met, the test is repeated with an additional 20 tubes.
In this case, the total number of particles in 30 tubes should not exceed 150, and not more than 3 tubes are
allowed to contain more than 8 particles .
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References
Dispensing for pharmaceutical by Cooper and gunn’s pg: 634-661
Modern dispensing pharmacy : N K Jain pg: 13.3-14.9
Text of pharmaceutical formulation : B.M Mithal pg: 268-278
British Pharmacopoeia. Published on behalf of Medicines and Health care products
Regulatory Agency; The department of Health, social services and public safety. Great
Britain sixth ed. 2010, volume IV.
United States of Pharmacopoeia 29 National formulary 24 (USP29–NF24) Supplement 1, is
current from April 1, 2006 through July 31, 2006.
http://www.authorstream.com/Presentation/irshadreza0786-2796089-ophthalmic-products-
formulation-evaluation/