This document discusses the importance of rheology in developing pharmaceutical formulations. Rheology considers how materials deform under stress, which directly impacts how drugs are formulated and how patients use medications. Viscosity and temperature dependence are key rheological concepts. Suspensions are multi-phase liquid dosage forms where particles are dispersed in a vehicle. Stabilizing suspensions requires controlling sedimentation, viscosity and rheology. Various excipients like thickeners, buffers, and preservatives are used to improve stability.
This slide contains the preformulation studies.It contains the various physicochemical properties that must be undergo to formulate the better absorption and stabiity of the different type of dosage form.This is ultimately used for the B Pharmacy final year students.Download the colourful ppt and enjoy the experience.
PHYSICAL AND CHEMICAL DEGRADATION OF PHARMACEUTICAL PRODUCTS.
Physical Factors
Loss of volatile constituents
Loss of water
Absorption of water
Crystal growth
Polymorphism changes
Colour changes
Chemical factors
Hydrolysis
Oxidation
Carboxylation
Decarboxylation
Isomerization
Polymerization
This slide contains the preformulation studies.It contains the various physicochemical properties that must be undergo to formulate the better absorption and stabiity of the different type of dosage form.This is ultimately used for the B Pharmacy final year students.Download the colourful ppt and enjoy the experience.
PHYSICAL AND CHEMICAL DEGRADATION OF PHARMACEUTICAL PRODUCTS.
Physical Factors
Loss of volatile constituents
Loss of water
Absorption of water
Crystal growth
Polymorphism changes
Colour changes
Chemical factors
Hydrolysis
Oxidation
Carboxylation
Decarboxylation
Isomerization
Polymerization
Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. This work reflects the improvement of Dissolution Characteristics as well as Bioavailability of poorly aqueous soluble drug Hydrochlorothiazide. It belongs to BCS class 2 i.e. it has poor water solubility but good permeability.
Methods of Solubility Enhancement bt Mr.Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Sub :- Biopharmaceutics & Pharmacokinetics
M.Pharmacy Sem 1
Savitribai Phule Pune University
Introduction :-
Solubility :-
“Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent.”
Solubalization :-
“ A Preparation of thermodynamically stable isotropic solution of a substance normally insoluble or slightly soluble in a given solvent by introduction of an additional component
Importance of Solubility :-
Therapeutic efeectivness of a drug depends upon the bioavailability & ultimately upon the solubility of drug molecules
Solubility is one of the important parameter to achieve desired concentration of a drug in systemic circulation for pharmacological ressponse to be shown.
Currently only 8% of new drugs have both high solubility & Permeability.
Nearly 40% of the new chemical entities currently being discovered are poorely water soluble
Methods :-
Spray freezing into liquid (SFL)
Ultra-Rapid Freezing
Kneading Technique
Co-precipitation
Solubalizing Agents
Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. This work reflects the improvement of Dissolution Characteristics as well as Bioavailability of poorly aqueous soluble drug Hydrochlorothiazide. It belongs to BCS class 2 i.e. it has poor water solubility but good permeability.
Methods of Solubility Enhancement bt Mr.Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Sub :- Biopharmaceutics & Pharmacokinetics
M.Pharmacy Sem 1
Savitribai Phule Pune University
Introduction :-
Solubility :-
“Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent.”
Solubalization :-
“ A Preparation of thermodynamically stable isotropic solution of a substance normally insoluble or slightly soluble in a given solvent by introduction of an additional component
Importance of Solubility :-
Therapeutic efeectivness of a drug depends upon the bioavailability & ultimately upon the solubility of drug molecules
Solubility is one of the important parameter to achieve desired concentration of a drug in systemic circulation for pharmacological ressponse to be shown.
Currently only 8% of new drugs have both high solubility & Permeability.
Nearly 40% of the new chemical entities currently being discovered are poorely water soluble
Methods :-
Spray freezing into liquid (SFL)
Ultra-Rapid Freezing
Kneading Technique
Co-precipitation
Solubalizing Agents
Liquisolid technique is a new
and promising method that can change the dissolution rate of drugs. It has been used to enhance
dissolution rate of poorly water-soluble drugs.
Orally Disintegrating Tablets (ODT) which disintegrates rapidly in saliva, usually within seconds,
without need for water. Drug dissolution, absorption, the onset of action and drug bioavailability
may be significantly increased better than those obtained from conventional dosage forms. combination of this two techniques is a promising approach for effective drug delivery
Formulation and Evaluation of Controlled Release Tablet of LamotrigineBRNSS Publication Hub
Controlled drug delivery [16] can be defined as delivery of the drug at a predetermined rate and/or to a
location according to the needs of the body and disease states for a definite time period. Controlled
release drug administration means not only the prolongation of the duration of drug delivery, similar to
the objective in sustained release and prolonged release, but the term also implies the predictability and
reproducibility of drug release kinetics. Oral controlled release drug delivery system is one that provides
continuous oral delivery of drugs at predictable and reproducible kinetics for a pre-determined period
throughout the course of GI transit.
Formulation and Evaluation of Liquisolid Compacts of CarvedilolIOSR Journals
The purpose of this study is to develop a novel liquisolid technique to enhance the dissolution rate of
poorly water soluble drug Carvedilol, a BCS class II drug, which is a β-blocker, by using different excipients.
The main components of a liquisolid system are a non volatile solvent, carrier and coating materials and a
disintegrant. Liquisolid system refers to the formulations that are formed by conversion of liquid drugs, drug
suspensions or drug solution in non-volatile solvents into dry, non adherent, free flowing and compressible
powder mixture by blending with suitable carrier and coating materials. Hence the dissolution step, a prerequisite
for drug absorption, is by passed and better bioavailability of poorly soluble drug is achieved.
Liquisolid tablets of carvedilol are prepared by using PEG, PG, glycerine as non volatile liquid vehicles and
Avicel PH 101 and 102, Aerosil as carrier and coating materials respectively. Optimized formulation containing
20% drug in PEG 400, with Avicel 101 as carrier and Aerosil as coating material has shown 98.4% drug
release within 20 min which is better than marketed product (CARCA 12.5mg, Intas). The DSC and X-RD
studies are performed to investigate the physicochemical properties of formulation and drug excipient
interactions. The results are found to be satisfactory
solubility enhancement and cosolvency by madhavishaikhazaroddin
“cosolvency and soluility enhancement” Pharmatech 2003, 160-166. They had developed simultaneous determination of sitagliptin phospate monohydrate and metformin by ultra performance liquid chromatographic (uplc)method.
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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.
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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
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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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).
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Target Audience
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Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. [Type text] Page 2
Dosage forms need specific flow properties so that they can be placed into a
container, remain stable over time, dispensed, handled and properly applied to the
affected area by patients. This is achieved by considering various physical and
analytical parameters.
RHEOLOGY
Rheology is the science that deals with the deformation of matters under the
influence of applied stresses.
Application of rheological principles has major importance in formulation and
analysis of pharmaceuticals as
it will directly affect the way a drug is formulated and developed,
the quality of the raw and finished product,
the drug efficacy,
the way a patient adheres to the prescribed drug,
the physical stability and bioavailability of formulations,
Overall healthcare cost.
Viscosity
Viscosity is a measure of a fluid’s resistance to flow i.e, the measure of a
substance’s resistance to motion under an applied force.
The following Stokes equation is familiar to most; expressing the rate of
sedimentation of suspended particles over time in a liquid vehicle:
Stokes Equation:
𝒅𝒚
𝒅𝒙
= d2
(pi – pe) g / 18ƞ
This equation estimates the sedimentation rate based on certain physical
characteristics of the suspension. These characteristics include the diameter of
suspended particles (d), acceleration due to gravity (g), density of the particles (ρi )
and external phase (ρe ), and the external vehicle viscosity (η).
3. [Type text] Page 3
Viscosity, is a characteristic non-Newtonian viscous, is an important material
property that contributes to a fluid’s performance. Thus, fluid pharmaceutical
products do not follow Newtonian flow.
Temperature dependence
Viscosity of a liquid decreases as the temperature increases and fluidity increases
with increase in temperature.
The dependence of viscosity on temperature is expressed by an analogous to an
Arhennius equation of chemical kinetics:
ƞ = AeEvRT
k = Rate constant
A = pre-exponential factor
Ev=activation energy
R=universal gas constant
T =absolute temperature (in Kelvin)
The Ev for the flow has been found to be one third of the energy of vaporization
and it needed a free space for flow. This is because a molecule can turn back and
maneuver in a small spacethan its actual size. More energy is required to break
4. [Type text] Page 4
bonds and permit flow in liquids composed ofmolecules that are associated
through hydrogen bonds. Thesebonds are broken at high temperature by thermal
movement, and Ev is decreased markedly.
Sedimentation:
Sedimentation means settling of particle (or) floccules occurunder gravitational
force in liquid dosage form.
Sedimentation Parameters:
Sedimentation volume (F) or height (H) for flocculatedsuspensions:
Sedimentation volume is a ratio of the ultimate volume of sediment (Vu) to the
original volume of sediment (VO) before settling.
F = V u / VO
Where, Vu = final or ultimate volume of sediment
Vo = original volume of suspension before settling
Degree of flocculation ( β )
It is the ratio of the sedimentation volume of the flocculated suspension F, to the
sedimentation volume of the deflocculated suspension, F ∞
β = (Vu/Vo) flocculated÷ (Vu/Vo) deflocculated.
The minimum value of ß is 1,when flocculated suspension sedimentation volume is
equal to the sedimentation volume of deflocculated suspension.
SUSPENSIONS
Suspensions are coarse dispersions that are biphasic liquid dosageforms of
medicaments in which the finely divided particles are dispersed in a vehicle.
The advantages of suspensions include,
5. [Type text] Page 5
Effective dispensing of hydrophobic drugs
Avoidance of the use of co-solvents
Masking of unpleasant taste of drugs
Easy swallowing for young and elderly patients.
Ideal features of suspensiondosage form
1. The final productshould be physically, chemically, and microbiologically stable.
2. Pharmaceutical suspensionshould be aesthetically pleasing and should also have a
pleasing odour, and taste.
3. The productmust remain sufficiently homogenous for at least the period between
shaking the container and removing the required amount.
4. Suspensions must not be too viscous to pour freely from a bottle or to flow through
a needle syringe (for injectable suspensions).
5. The drug substancemust not recrystallize and/or change its polymorphic form
during storage.
6. Suspended particles should settle slowly and the sediment or creaming produced
on storage, if any, should readily redisperse upon gentle shaking of the container.
7. Parenteral and ophthalmic suspensions should be sterilizable and syringable (for
parenteral suspensions).
Stability of suspensions:
Flow behavior of a suspension system is not only dependent on the dispersed phase
(particle size, shape, morphology, concentration), but also crucially dependent on
the rheology modifiers which are used in pharmaceutical suspensions to enhance
their stability.
Rheologic modifiers
Rheologic modifiers are organic and inorganic coating adds that controlthe
rheological characteristics of liquid formulations. In coating technology, rheology
modifiers are mainly used to provide either pseudoplastic and thixotropic
properties. It includes binders (polymers, oligomers, reactive dilutants), solvents
(organic, aqueous), pigments (organic, inorganic) and fillers and additives
(stabilizers, inhibitors, catalysts).
6. [Type text] Page 6
Buffer and pH modifying agents:These agents are added to stabilize the
suspensions by controlling the altering pH conditions. Citrate buffer are used to
stabilize suspensions in the range pH 3-5 phosphatebuffers are used to stabilize
suspensions in the range of pH 7-8.
Thickeners/Viscositymodifiers: these agents are used to increase the viscosity of
a suspension without substantially changing its other properties and decreases
sedimentation. They can be hydrophilic colloids or polymers.
Polymers of high molecular weight and composed ofwater-loving functional
groups can greatly help to controlviscosity, rheology and thus, stabilizing the
formulation. However, the interaction of these polymers with an aqueous medium
will crucially depend on the nature of the aqueous medium. E.g., gum acacia, corn
starch.
Flocculating agents:Addition of flocculating agents help to stabilize the
suspension by decreasing inter-particle attraction which helps to prevent
aggregation and caking overtime. Eg, Aluminium chloride is used as a flocculating
agents at concentrations of 0.01%-1%.
Coloring agents:They are added to impart distinctive color to suspension and
improve elegance. Eg, D&C Yellow#10 in Ibuprofen suspension.
Wetting agents:Surfactants or Wetting agents are used in suspension to reduce
the interfacial tension between solid particles and vehicle thereby promoting
wetting and deflocculation of particles. E.g., glycerin.
Preservatives:They are added to prevent microbial growth in formulated
suspensions. Eg, Propylene glycol.
7. [Type text] Page 7
Ciproxin 250 mg/5 mL granules and solvent for oral suspension
Activeingredient – ciprofloxacin
Used as - Antibiotic, Antiprotozoal medication.
Inactiveingredients:
Sweetening agent - Sucrose/Neotame-3to10% concentration
Flavoring agent - mixed fruit powder (orange, banana, pineapple, strawberry)-0.2
to 1% concentration
Buffering agents – sodium citrate, potassium phosphate, citric acid – 0.2 to 1%
concentration
Suspending agent- Xanthan gum, sodium CMC, hydroxypropyl cellulose-0.1-
0.5% concentration
Suitable solvent- Isopropyl alcohol, methylene chloride, water
Lubricants - magnesium sterate, sodium steryl fumarate 0.05-0.2%
8. [Type text] Page 8
Other excipients - cellulose, starch, lactose 0-15%
Vehicle - purified water
Co-solvent- glycerin
REFERENCE:
http://www.sips.org.in/wp-content/uploads/2020/03/SUSPENSION-
_BP103TP.pdf
file:///C:/Users/VM-MED/Downloads/rheology-in-pharmaceutical-
formulationsa-perspective-2329-6631.1000108%20(2).pdf
Mastropietro DJ, Nimroozi R, Omidian H (2013) Rheology in
Pharmaceutical Formulations-A Perspective. J Develop Drugs 2: 108.
doi:10.4172/2329-6631.1000108
Martin’s Physical Pharmacy and Pharmaceutical sciences by Patrick J. Sinko
Physical pharmaceutics by Manavalan and Ramasamy.
file:///C:/Users/VM-MED/Downloads/rheology-in-pharmaceutical-
formulationsa-perspective-2329-6631.1000108%20(2).pdf