Drug-excipient compatibility studies are important to identify compatible excipients for drug formulations. Compatibility can be tested using various analytical techniques including thermal methods like DSC and DTA, accelerated stability studies, spectroscopy like FTIR, and chromatography like TLC. Incompatibilities are identified by changes in thermal behavior, degradation of the drug, or appearance of new peaks in analytical tests. Common techniques involve storing drug-excipient mixtures under accelerated conditions and monitoring the samples for physical or chemical changes over time. The results of compatibility studies provide critical information for formulation development and regulatory filings.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
Evaluation methods for drug excipients and container interactionSagar Savale
Excipients are one of the three components that in combination produce the medicine that the patient will take.
In therapeutic terms, the API is of primary importance because without it there is no treatment and no product.
In term of drug manufacturing all three of them are equally important so we cannot neglect anyone of them.
The interactions between excipients and the other two components (the API and the manufacturing process), and/or between two or more excipients, are fundamental to the transformation of an API into a medicinal product.
Drug excipient incompatibilities are major concerns in formulation development.
Selection of the proper excipient during preformulation studies is of prime importance.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
Dissolution, factors affecting drug dissolution, methods to evaluate dissolution, advantages and disadvantages, recent approaches--these are the topics covered in this presentation.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
Evaluation methods for drug excipients and container interactionSagar Savale
Excipients are one of the three components that in combination produce the medicine that the patient will take.
In therapeutic terms, the API is of primary importance because without it there is no treatment and no product.
In term of drug manufacturing all three of them are equally important so we cannot neglect anyone of them.
The interactions between excipients and the other two components (the API and the manufacturing process), and/or between two or more excipients, are fundamental to the transformation of an API into a medicinal product.
Drug excipient incompatibilities are major concerns in formulation development.
Selection of the proper excipient during preformulation studies is of prime importance.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
Dissolution, factors affecting drug dissolution, methods to evaluate dissolution, advantages and disadvantages, recent approaches--these are the topics covered in this presentation.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
Introduction,Drug- Excipient Compatibility Experimental Design ,Excipient role in drug destabilization,DRUG EXCIPIENT COMPATIBILTY IN PARENTERAL PRODUCTS.This topic are described.
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
- 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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
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Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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.
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DEFINITIONS:
1. DRUG:
2. EXCIPIENTS:
INTRODUCTION:
An incompatibility may be defined as…..
“An undesirable drug interaction with one or more components of a formulation, resulting in
changes in physical, chemical, microbiological or therapeutic properties of the dosage form.”
An incompatibility in dosage form can result in any of the following changes:
change in colour/appearance;
loss in mechanical properties (e.g., tablet hardness)
changes to dissolution performance;
physical form conversion;
loss through sublimation;
a decrease in potency; and
increase in degradation products.
Excipient compatibility studies are conducted mainly to predict the potential incompatibility of
the drug in the final dosage form.
These studies also provide justification for selection of excipients, and their concentrations in the
formulation as required in regulatory filings.
There fillings has also been an increased regulatory focus on the Critical Quality Attributes
(CQA) of excipients and their control strategy, because of their impact on the drug product
formulation and manufacturing process which enhanced due to increasing QbD trend.
OBJECTIVE
These studies are important in the drug development process, as the knowledge gained from
excipient compatibility studies is used to
Select the dosage form components,
Delineate stability profile of the drug,
Identify degradation products, and
Understand mechanisms of reactions.
If the stability of the drug with the excipients are found to be unsatisfactory, strategies to mitigate
the instability of the drug can be adopted.
IMPORTANCE OF DECS:
Stability of the dosage form can be maximized
It helps to avoid the surprise problems
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Drug discovery can emerge only new chemical entity
DECS data is essential for IND
Determine a list of excipients that can be used in final dosage form
COMPATIBILITY TESTING:
Aspects of compatibility tests are:
Identification of compatible excipient for a formulation
Identification of stable storage conditions for drug in solid or liquid state
Compatibility tests are categorised as:
1. Compatibility test for solid state reactions
o much slower and difficult to interpret
2. Compatibility test for liquid state reactions
o easier to detect
o According to Stability Guidelines by FDA, following conditions should be
evaluated for solutions or suspensions:
1. Acidic or alkaline pH
2. Presence of added substances
3. High oxygen and nitrogen atmospheres
4. Effect of stress testing conditions
Typical Modalities of Compatibility Testing
a) Study Execution
b) General Steps and decisions
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General Steps in Compatibility Studies:
1. Experimental Design
2. Sample preparation
3. Storage
3. Sample Analysis & Data Interpretation
I. Experimental Design
o The design of experiments is governed by the potential formulation choices, and
excipient preferences.
o These decisions are made in conjunction with all the other available preformulation data,
API characteristics, and marketing preferences.
o These also determine the types of pharmaceutical excipients that are evaluated.
Ex: compatibility studies for a liquid formulation of an insoluble compound would
differ widely, and include excipients such as surfactants and suspending agents, from the
studies designed for a highly soluble compound.
o Compatibility studies are commonly carried out by accelerated stress testing, and
evaluation of its effect on the binary or multicomponent drug–excipient mixtures.
o Designs:
i. Two- or Multi-component Systems
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Binary mixtures of drug and common pharmaceutical excipients such as
diluents or ternary mixtures of drug, a diluent, and excipients used in lower
proportions such as disintegrants and lubricants.
And are incubated at accelerated conditions of temperature and humidity
for extended periods of time, using drug alone and excipient alone as
controls.
Incompatibilities are physically identified by
Visual observation for color or physical form changes,
Spectroscopic and calorimetric methods, and
Chemically quantified by analytical assays for drug content and
impurities.
ii. n-1 Design & Mini formulations
Compatibility studies are often aimed at solving formulation stability
issues.
In such cases studies are carried out with the exclusion of only one
component in each sub-lot to identify the source of incompatibility.
Often, mini-formulations are prepared with the exclusion of non-critical,
quantitatively minor, and/or easily interchangeable ingredients, e.g., colors
and flavors, from solutions and suspensions.
II. Sample Preparation
a. For solid state reactions:
Sample A: -mixture of drug and excipient
Sample B: -Sample + 5% moisture
Sample C: -Drug itself without excipients
o All the samples of drug-excipient blends are kept for 1-3 weeks at specified storage
conditions.
o Then sample is physically observed.
o It is then assayed by TLC or HPLC or DSC
o Whenever feasible, the degradation product are identified by MASS SPECTROSCOPY,
NMR or other relevant analytical techniques.
b. For liquid state reactions:
o Place the drug in the solution of additives.
o Both flint and amber vials are used.
o This will provide information about
-Susceptibility to oxidation.
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-Susceptibility to light exposure.
-Susceptibility to heavy metals.
o In case of oral liquids, compatibility with ethanol, glycerin, sucrose, preservatives and
buffers are usually carried out.
III. Storage Conditions
o The storage conditions used to examine compatibility can vary widely in term of temp. &
humidity, but a temp. of 50°C for storage of compatibility sample is considered
appropriate.
o Some compounds may require high temp. to make reaction proceed at a rate that can be
measured over a convenient time period.
IV. Sample Analysis & Data Interpretation
o Monitoring Drug Degradation
Thermal Methods (DSC, DTA, etc.)
o Monitoring to form changes
PXRD, ssNMR, NIR spectroscopy, etc.
o Data analysis
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Compatibility Studies in Different Dosage Forms
SOLID DOSAGE FORMS:
In case of Tablets, The various excipients used are as follows:
a. Diluents /fillers:
Ex. Lactose, dibasic Ca.phosphate, sucrose, glucose, mannitol, sorbitol
b. Binders :
Ex. PVP, cellulose, MCC, sorbitol, gelatine, PEG
c. Disintegrants:
Ex. PVP, Sodium CMC, sodium CMC, sodium starch glycolate
d. Anti-adherents:
Ex. Magnesium stearate
e. Lubricants:
Ex. Talc, Mg.stearate
f. Glidants:
Ex. Magnesium carbonate
g. Coating Agents
Ex: HPMC, HPMCP, EC
EXCIPIENT EXAMPLE INCOMPATIBILITY REASON
DILUENT
Lactose Primary and secondary
amines
Reducing sugar
Mannitol Omeprazole sodium,
primaquine
Crystallization
Dicalcium
phosphate
dihydrate
temazepam Alkaline nature
BINDERS PVP Haloperidol, ranitidine
Hcl
Peroxides
DISINTEGRANT Starch Strongly oxidising subs Reducing sugar
ANTI-
ADHERENT
Mg.stearate Aspirin Undesirable product is
formed
LUBRICANTS Talc Quaternary ammonium
compds.
GLIDANTS Magnesium
carbonate
Phenobarbital sodium Acids dissolve MgCO3
COATING AGENT INCOMPATIBILITY INTERACTION
HPMC Oxidizing agents
SPLITING OF FILM
HPMCP MCC and calcium CMC
ETHYL
CELLULOSE
Paraffin wax
Microcrystalline wax
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Maillard Reaction:
LIQUID DOSAGE FORMS:
1. PARENTERALS
o The various excipients used in parenteral preparations are
I. Anti-oxidants:
Ex. Ascorbic acid, Na bisulphite, EDTA
II. Preservatives:
Ex. Methyl paraben, propyl paraben
III. Cosolvents:
Ex. Sorbitol, glycerol, PEG
IV. Chelating agents:
Ex. EDTA
V. Tonicity agents:
Ex. sod. Chloride, pot. Chloride, dextrose.
EXCIPIENT EXAMPLE INCOMPATIBILITY REASON
Antioxidant
Ascorbic acid Penicillin G, Phenylephrine
Hcl
Acid unstable
Na. bisulfite Sympathomimetics/ o or p-
hydroxy benzyl alcohol
Sulphonic acid
derivative
Preservatives Phenyl-mercuric acetate Halide ions Less soluble
hydrogen
Co solvents
Polyethylene glycol Aspirin, carbonic acid,
theophylline derivatives
Peroxide impurity
Glycerin Phenols, salicylates, tannin Iron impurity
Chelating agents Edetate salts Zn insulin, thiomersal,
amphotericin
Tonicity agents
Sodium chloride Silver ,lead, mercury salts
Dextrose Strong alkali ,
cyanacobalamine ,warfarin
Brown coloration
and decomposition
,loss of clarity
Amine +Reducing
sugar
condensation Water+ketosamine
5(hydroxy methyl)-2
furaldehyde
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2. AEROSOLS
Example: Interaction of propellant-11 with aqueous drug products
o Propellant 11 is trichloromonofluoromethane.
o Interaction of propellant 11 with aqueous drug is as follow
o Therefore, propellant 11 is incompatible with aqueous drug products.
Analytical Techniques for DECS
1. Thermal method of analysis
a) DSC- Differential scanning calorimetry
b) DTA- Differential thermal analysis
2. Accelerated stability studies
3. FT-IR SPECTROSCOPY
4. DRS- Diffuse reflectance spectroscopy
5. Chromatography
a) TLC-Thin layer chromatography
b) SIC -Self interactive chromatography
6. Miscellaneous
a) Fluorescence spectroscopy
b) Vapour pressure osmometry
DSC – DIFFERENTIAL SCANNING CALORIMETRY
DSC is widely used to investigate and predict any physico-chemical interaction between drug and
excipients involving thermal changes.
DSC is the measurement of rate of heat evolved or absorbed by the sample, during a temperature
programme.
METHOD:
The preformulation screening of drug-excipient interaction requires (1:1) Drug:excipient
ratio, to maximize the likehood of observing an interaction.
Mixture should be examined under N2 to eliminate oxidative and pyrrolytic effects at heating
rate (2, 5 or 100 C / min) on DSC apparatus.
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However, some changes in peak shape and peak height and width are expected because of
possible differences in mixture geometry.
Example : Ofloxacin
Experimental excipients: Lactose, Starch, PVP, Talc
How to
detect
interaction
by DSC
Appearance
of new peak
Elimination of
endothermic
peak
Area of
peak/enthalpy
Melting point/peak
temperature
Change
in peak
shape
Onset of a
peak
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LIMITATIONS OF DSC:
If thermal changes are very small, DSC can’t be used.
DSC can not detect the incompatibilities which occur after long term storage.
E.g. MCC / ASPIRIN
Not applicable if test material exhibits properties that make data interpretation difficult.
ADVANTAGES:
o Fast
o Reliable and very less sample required.
DTA – DIFFERENTIAL THERMAL ANALYSIS
Thermal Analysis is useful in the investigation of solid-state interactions.
It is also useful in the detection of eutectics.
Thermograms are generated for pure components and their physical mixtures with other
components.
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In the absence of any interaction, the thermograms of mixtures show patterns corresponding to
those of the individual components.
In the event that interaction occurs, this is indicated in the thermogram of a mixture by the
appearance of one or more new peaks or the disappearance of one or more peaks corresponding to
those of the components.
ACCELERATED STABILITY STUDIES
Different formulations of the same drug are prepared.
Samples are kept at 40ºC / 75 % RH.
Chemical stability is assessed by analyzing the drug content at regular interval.
Amt. of drug degraded is calculated.
% Drug decomposed VS time(month) is plotted.
Ex: Experimental drug: Enalapril maleate
Experimental excipients: (Directly compressible diluents):
1. Avicel
2. Spray dried lactose
3. Emcompress
4. A-tab
NOTE: In all the formulations excipients other than directly compressible vehicle are kept same.
Formulation DTA Shelf life Inference
F1(AVICEL) + 3½ months Least stable
F2(SPRAY DRIED
LACTOSE)
_ 1 year and 3 months Ideal
F3(EMCOMPRESS) + 8 months Not recommended
F4(A-TAB) + 9½ months Not recommended
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SELF-INTERACTIVE CHROMATOGRAPHY
SIC is useful for proteinous drug and excipients.
METHOD:-
SIC is a modified type of affinity chromatography.
Here, drug is made immobilized as the SP & soln. to be tested( excipient soln.) acts as MP.
Measure Rt (Retention time) & compare with non –retained marker.
PRINCIPLE:-
For different mobile phases (i.e. different excipients) the injected drug have different interactions
(may be repulsive or attractive) with the SP of drug leads to shift in retention time.
FTIR
In FTIR technology, the presence of a peak at a specific wave number indicates the presence of a
specific chemical bond.
If specific interactions took place between the materials, the most obvious and significant
difference would be the appearance of new peaks or a shift of existing peaks.
It is used to study the interaction occurring between drug and excipient by matching the peaks of
spectra.
The absence of any significant change in the IR spectral pattern of drug & polymer physical
mixture indicated the absence of any interaction between the drug and the excipient.
Ex: Moxifloxacin
Experimental Excipients: PLGA
The IR-spectra of the physical mixture of both drug and polymer exhibited all the characteristics
peaks as shown.
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Therefore, it shows compatibility of drug with the polymer.
All the spectra acquired were scanned between 400 and 4000 cm-1
at a resolution of 4 cm-1
.
TLC & HPTLC
TLC is generally used as confirmative test of compatibility after performing DSC.
S.P. consist of powder (Silica, Alumina, Polyamide, Cellulose & Ion exchange resin) adhered onto
glass, plastic or metal plate.
Solution of Drug, Excipient & Drug: Excipient mixture are prepared & spotted on the same
baseline at the end of plate.
The plate is then placed upright in a closed chamber containing the solvent which constitutes the
M.P.
15. Worked by Ayesha (Extended by Suraj C)
PPM
15
The material is identified by its Rf value.
The position of the material on the plate is indicated by spraying the plate with certain reagents or
exposing the plate to UV radiation.
If there is no interaction between drug & excipient, the mixture will produce two spots.
The Rf value of which are identical with those of individual drug & excipient.
If there is interaction, the complex formed will produce a spot.
The Rf value of which is different from those of the individual components.
FLUORESCENT MEASUREMENT
This technique is restricted to those compounds, which can generate florescence.
As the no. of such compounds are restricted, this method is used in Analysis and not in
preformulation.
INCOMPATIBLE IMPURITIES
Chemical impurity profiles
Chemical impurity profiles of the excipient can be very important in influencing the long term
chemical stability performance of the formulated drug product.
E.g..
(1)DCP – Sometimes, IRON may be present in DCP as impurities. & it is incompatible with
MECLIZINE HCl (Fe NMT 0.04%).
(2)Hydroperoxides (HPO) - Evaluation of Hydroperoxides ( HPO) in common
pharmaceutical excipients:
POVIDONE
PEG 400
HPC
POLYSORBATE 80
Contains substantial conc. of
HPOs with significant batch to
batch OR manufacturer to
manufacture variations
16. Worked by Ayesha (Extended by Suraj C)
PPM
16
o While MCC, Lactose, High mol. Wt. PEG contains less amt. of HPOs.
o In solid dosage forms, PVP is commonly used as a bonder for wet granulation & often
used at very low conc.
o However, the total HPO content is high enough in PVP to promote significant
degradation when formulating oxidatively sensitive drugs.
o 5% of PVP was shown to be responsible for N-oxide formation of Raloxifen HCl, due
to high HPO content.
o So for these excipients, active monitoring and control of HPOs by the supplier may be
necessary.
(3)Iron (Fe) - Gelatin is also containing IRON as impurities
o Dark spots may occur in the shell due to the migration of water soluble iron sensitive
ingredients from fill material into the shell.
REFERENCES
Qui Y. et.al; Developing Solid Oral Dosage Forms; Elsevier Academic Press, 125-143, 2011.
Leon Lachman & Liberman; Pharmaceutical Dosage forms 2010.
Hand book of Pharmaceutical Excipients, 2011.
Modern Pharmaceutics by Banker & Rhodes, 4th edition, 2002.
I.J.P.E., Vol 1, 2002
J.Ph.Sci, Vol 97, 106-110; 2007.