new Puneet PPT On Formulation & Evalution of Nano-Suspension of Carvedilol.pptx
1. Rajasthan University of Health Sciences, Jaipur (Rajasthan)
In partial fulfillment for the award of the degree of
Master of Pharmacy in Pharmaceutics
A thesis presentation submitted to the
Under the guidance of Supervisor:
Mr. SUNIL KUMAWAT, M.Pharm
Associate Professor,
Department of Pharmaceutics
Submitted by
NAME: PUNEET KUMAR MAHARSHI
Enrollment No. 2006/14512
June 2025
GOENKA COLLEGE OF PHARMACY
Formulation and Evaluation of Nanosuspension
of Carvedilol
2. Nanosuspension are aqueous suspensions containing one or several submicron
colloidal system which consists of poorly water-soluble drug, suspended in an
appropriate dispersion medium stabilized by surfactants and also contain
appropriate stabilizers.
stabilizer can added to reduce the free energy of the system by decreasing
interfacial tension and to prevent nanoparticle aggregation by electrostatic or steric
stabilization. Stabilizer constitutes an integral part of nanosuspensions and it is
important to understand their role on physical stability of nanosuspension.
Stabilizers include excipients that enable nanogrinding of the drug particles,
prevent crystal growth or nanoparticle aggregation during storage, pH-buffering
substances, and preservatives.
Commonly used polymeric stabilizers for nanosuspensions include cellulose ethers,
such as hydroxyl propyl cellulose (HPC) and hydroxyl propyl methylcellulose
(HPMC), povidone, and poloxamers (types 188, 407 and 338).
1. Introduction of Nanosuspension
3. Advantages of Nanosuspension:
1. Enhance the solubility and bioavailability of drugs
2. Suitable for hydrophilic drugs
3. Higher drug loading can be achieved
4. Dose reduction is possible
5. Enhance the physical and chemical stability of drugs
6. Provides a passive drug targetes
7. Provides ease of manufacture and scale-up for large scale production.
8. Long-term physical stability due to the presence of stabilizers.
9. Rapid dissolution and tissue targeting can be achieved by IV route of
administration,
10. Reduction in tissue irritation in case of subcutaneous/intramuscular
administration.
11. Higher bioavailability in case of ocular administration and inhalation delivery.
12. Drugs with high log P value can be formulated as nanosuspensions to increase
the bioavailability of such drugs
4. Biopharmaceutics Classification System
For the most part, the instant release (IR) solid oral dosage
forms were the primary focus of the development of the
biopharmaceutical categorization system. In the scientific community, it is
the framework for categorizing pharmacological compounds according to
their permeability to the digestive tract and their capacity to dissolve in
water.7
It is a technique for the development of drugs that enables
evaluation of the contributions of three important parameters, namely
dissolution, solubility, and intestinal permeability, which have an effect on
the oral drug absorption from quick release solid oral dosage forms.
There is a significant amount of interest in this categorization system
primarily due to the fact that it can be utilized in the early stages of
medication development and subsequently in the management of
product modification throughout the cycle of its life. The guideline paper
on immediate release solid oral dosage forms was the first place where it
was incorporated into the process of making decisions on regulatory
compliance: Adjustments made after approval and scaling up.8
5. Rational of developing drug nanosuspensions
There is a lack of efficiency in the present methods used to create new
pharmaceutical goods. There are around 250 compounds that make it
into the preclinical program for every 5,000–10,000 molecules that enter
the R&D pipeline. Out of those, five make it into clinical trials, and only
one is approved for market introduction. The primary causes of expenses,
which can vary from 0.8 to 2 billion dollars, are the failure of a novel
molecule at the late pre-clinical stage and the growing costs of phases 1
to 3 of clinical trials. These factors contribute to the overall expense of
bringing a new therapeutic substance to market.
A pharmaceutical product must meet the current standards of health
regulatory agencies throughout its development, from discovery to
marketing and post-marketing. Pharmaceutics must have constant
important quality qualities such dosage consistency, drug solubility, and
storage stability, as well as a stable and robust production process, to
guarantee quality, effectiveness, and safety. New molecule synthesis and
in vitro bioactivity testing have been considerably accelerated by the
increased use of combinatorial chemistry, phage display libraries, and
high-throughput screening.
6. Methods of Preparation For Nanosuspensions:
A. Milling techniques (Nanocrystals or Nanosystems) Media milling:
Media milling is a method that is utilized in the process of preparing
nanosuspensions. 19
Nanocrystal is a technology that was invented by Liversidge
and colleagues and is protected by a patent. The medication is milled through a
medium in this method, which results in the formation of nanoparticles of the
targeted substance. The microparticulate drug is disintegrated into nanosized
particles with the application of high energy and shear forces that are created as
a consequence of impaction of the milling media with the drug. This provides
the necessary energy input. During the process of media milling, the milling
chamber is loaded with the milling medium, water or an appropriate buffer, the
medication, and the stabilizer. In the following step, the milling medium or pearls
are spun at a shear rate that is extremely high. The most significant issue that
arises with this approach is the possibility that the grinding medium residues
that are left behind in the final product might cause difficulties in terms of
administration. 19
7. B. Dry co-grinding:
Wet grinding procedures include the preparation of nanosuspensions by high
pressure homogenization and media milling using a pearl-ball mill.
Nanosuspensions have recently been able to be created through the use of dry
milling processes. Following dispersion in a liquid medium, it has been reported
that successful work has been done in the manufacture of stable
nanosuspensions by the use of dry-grinding of weakly soluble medicines coupled
with soluble polymers and copolymers. (41–42)
Grinding with polyvinyl pyrrolidone (PVP) and sodium dodecyl sulfate (SDS)
resulted in the development of colloidal particles of a number of medications
that are not very water soluble. These pharmaceuticals include griseofulvin,
glibenclamide, and nifedipine. Itoh et al. described the formation of these
colloidal particles. There have been a great number of soluble polymers and co-
polymers utilized, including polyvinyl alcohol (PVP), polyethylene glycol (PEG),
hydroxyl propyl methylcellulose (HPMC), and derivatives of cyclo-dextrin. 35–37
8. C. Precipitation Method:
The medication is dissolved in an organic solvent and then combined with a
miscible anti-solvent using a precipitation process. The medication precipitates
out of water-solvent mixtures due to its poor solubility. There is a wide range of
mixing procedures. There has also been a combination of strong shear
processing with precipitation. The nanoedge method, which is owned by Baxter
International Inc. and its subsidiaries, uses high shear and/or heat energy to
precipitate friable materials, which are then fragmented.
9. D. Supercritical fluid method:
Nanoparticles can be manufactured from pharmaceutical solutions using
supercritical fluid technology. The many approaches that were tried out included
the supercritical anti-solvent process, precipitation with compressed anti-
solvent, and rapid expansion of supercritical solution (RESS). As the drug solution
in supercritical fluid is forced to expand via a nozzle in the RESS, the solvent
power of the fluid is reduced, and the drug is precipitated as small particles.
The PCA approach involves atomizing the medication solution and then placing it
in a chamber with pressurized carbon dioxide. The solution becomes
supersaturated upon solvent removal, leading to the precipitation of fine crystals
144.
In the supercritical anti-solvent procedure, a medication that is not very soluble
in a supercritical fluid is combined with a solvent that is both miscible with the
fluid. After being injected into the supercritical fluid, the drug solution becomes
supersaturated as the solvent is removed by the fluid. Fine crystals of the
substance are then precipitated.
10. E. Post-Production Processing:
When the drug candidate is very vulnerable to hydrolytic cleavage or chemical
degradation, post-production processing of nanosuspensions becomes a critical
step in the process. Processing may also be necessary in situations when the
nanosuspension cannot be stabilized for an extended period of time using the
best feasible stabilizer, or when there are acceptability limits in relation to the
route that is sought.
In light of these considerations, it is possible to accomplish the production of a
dry powder consisting of nano-sized drug particles by employing methods such
as lyophillization or spray drying.
When it comes to these unit activities, rational selection is required, taking into
consideration the characteristics of the medicine as well as the cost elements.
11. Methods of Preparation For Nanosuspensions:
1. Milling techniques (Nanocrystals or Nanosystems) Media milling
2. Dry co-grinding
3. High Pressure Homogenization: (HPH)
a. Homogenization in Aqueous media (Dissocubes)
b. b. Homogenization in Non Aqueous Media (Nanopure)
4. Precipitation Method
5. Supercritical fluid method
6. Post-Production Processing
12. 2. REVIEW OF LITERATURE
Aldeeb et al., (2024) nanosuspensions have emerged as a promising solution for
addressing the bioavailability challenges of hydrophobic drugs with poor solubility in
both aqueous and organic environments. By enhancing drug solubility and
absorption, nanosuspensions offer significant potential in improving drug delivery,
particularly for topical applications such as ocular, pulmonary, and dermal
treatments. Among these, nanocrystals have gained attention for their ability to
increase skin adhesiveness, saturation solubility, and dissolution rates, thereby
improving cutaneous bioavailability for low-to-medium solubility drugs.
Redon, J et al.,(2024) High blood pressure (HBP) is the leading cause of mortality and
years of disability, and its prevalence is increasing. Therefore, diagnosis and effective
treatment of HBP is one of the main goals to prevent and reduce its complications,
and pharmacological treatment is the cornerstone of hypertension management.
The gradual introduction of different drug families has led to the development of
new molecules that have improved efficacy and reduced adverse effects.
13. Narla, D. et al., (2024)Orodispersible films (ODF) represent an innovative
approach in drug delivery systems, offering solutions to enhance patient
compliance and address challenges associated with traditional dosage forms.
Particularly beneficial for patients with swallowing difficulties, ODFs can be easily
ingested without the need for water, chewing, or swallowing. Carvedilol,
characterized by low bioavailability due to hepatic first-pass metabolism,
prompted the focus of this research on developing carvedilol ODFs to enhance its
bioavailability.
Zhang, M et al., (2024) This study investigated the solubility, oil–water
distribution coefficient, and dissociation constant of Isoxanthohumol (IXN) and
formulated IXN nanoparticles (IXN-Nps) using micro media grinding.
Characterization revealed an average particle size of 249.500 nm, a polydispersity
index of 0.149, and a zeta potential of −25.210 mV. Mannitol (5%) was identified
as the optimal cryoprotectant. Compared to IXN, IXN-Nps exhibited a threefold
decrease in the half-maximal inhibitory concentration, significantly inhibiting HT-
29 colon cancer cells.
14. Kolipaka, T et al., (2023) Posaconazole (PSZ), an anti-fungal drug, has broad-
spectrum activity. But its action is limited due to the poor solubility of
posaconazole. The objective of the present study was to formulate and optimize
posaconazole nanosuspension using a wet milling process. Final product quality
was assured by a Quality by Design (QbD) approach that evaluated the impact of
critical material attributes (CMAs) and critical process parameters (CPPs) on the
critical quality attributes (CQAs) of the nanocrystals.
Chiclana et al., (2023) Carvedilol (CARV) is an ‘off-label’ β-blocker drug to treat
cardiovascular diseases in children. Since CARV is nearly insoluble in water, only
CARV solid forms are commercialized. Usually, CARV tablets are manipulated to
prepare an extemporaneous liquid formulation for children in hospitals. We
studied CARV to improve its aqueous solubility and develop an oral solution. In
this study, we assessed the solubility and preliminary stability of CARV in
different pH media. Using malic acid as a solubility enhancer had satisfactory
results. We studied the chemical, physical, and microbiological stability of 1
mg/mL CARV–malic acid solution.
15. 3. DRUG PROFILE
Carvedilol:
Generic name:- carvedilol
Chemical formula: - C24
H26
N2
O4
Molecular weight: - 513.5 gm/mol.
Chemical name: (±)-[3-(9H-carbazol-4-yloxy)-2—hydroxypropyl]-[2-
(2methoxyphenoxy)ethyl]amine
Category: - Antihypertensive activity.
Half life: 7-10 hour
Dose: 3.125 to 25 mg. twice a day
Description: A white or almost crystalline powder
Solubility: sparingly soluble in water and soluble in methanol.
Melting point: 114-1150
c.
Bioavailability: 25% - 35%
Mechanism of Action: Carvedilol is a racemic mixture in which nonselective β-
adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic
blocking activity is present in both R(+) and S(-) enantiomers at equal potency.
16. Metabolism and Excretion:
The metabolization of carvedilol is rather significant. Following the oral
administration of radiolabeled carvedilol to healthy volunteers, the amount
of carvedilol that accounted for the total radioactivity in plasma was only
around seven percent, as determined by the area under the curve (AUC). In
the urine, less than two percent of the dosage was discharged in its original
form. Carvedilol is largely metabolized by the formation of glucuronidation
and the oxidation of aromatic rings.
A further metabolization of the oxidative metabolites occurs by conjugation,
which is accomplished through glucuronidation and sulfation. The
metabolites of carvedilol are mostly eliminated from the body through the
bile and expelled in the feces. The phenol ring undergoes demethylation and
hydroxylation, which results in the production of three active metabolites
that possess the ability to inhibit β-receptors. In terms of β-blockage, the 4'-
hydroxyphenyl metabolite has been shown to be roughly thirteen times
more effective than carvedilol, according to the findings of preclinical
research.
17. Pharmacokinetics:
Absorption: The oral administration of immediate-release carvedilol tablets
results in the quick and wide absorption of carvedilol. The absolute
bioavailability of carvedilol is around 25–35 percent, which is attributed to a
considerable amount of first-pass metabolism. Extended-release capsules of
COREG CR provide about 85 percent of the bioavailability of tablets of
carvedilol that are taken immediately after administration.
Distribution: Carvedilol is predominantly linked to albumin, which accounts
for more than 98% of its binding to plasma proteins. There is no correlation
between the concentration of the plasma and the plasma-protein binding
over the therapeutic range. Carvedilol is a lipophilic molecule that is basic in
nature. It has a steady-state volume of distribution of around 115 L, which
indicates that it is distributed into extravascular tissues to a significant
degree.
18. Drug-drug interaction:-
The following drug interaction studies were performed with immediate-
release carvedilol tablets.
Amiodarone: Pharmacokinetic research was carried out on 106 Japanese
patients who were suffering from heart failure. The study found that the
coadministration of modest loading and maintenance doses of amiodarone
with carvedilol led to a rise in the steady-state trough concentrations of S(-)-
carvedilol that was at least two times higher than the initial concentrations.
Cimetidine: The steady-state area under the curve (AUC) of carvedilol was
raised by thirty percent when cimetidine (1,000 mg/day) was administered
to ten healthy male individuals in a pharmacokinetic trial. However, there
was no change in the Cmax.
19. Digoxin: In 12 hypertensive individuals, the steady-state area under the
curve (AUC) and trough concentrations of digoxin rose by 14% and 16%,
respectively, after the concurrent treatment of carvedilol (25 mg once daily)
and digoxin (0.25 mg once daily) over a period of 14 days.
Warfarin: Carvedilol, at a dosage of 12.5 milligrams twice day, did not have
any impact on the steady-state prothrombin time ratios, nor did it change
the pharmacokinetics of R(+)- and S(-)-warfarin when it was administered
concurrently with warfarin in a group of nine healthy volunteers.
Indication & Usage:
Carvedilol is intended for the treatment of mild to severe heart failure of
ischemic or cardiomyopathic origin during congestive heart failure. It is
typically used in conjunction with diuretics, ACE inhibitors, and digitalis in
order to improve the patient's chances of survival and also to decrease the
likelihood of hospitalization (for more information, see clinical trials).
20. Carvedilol is indicated for the treatment of left ventricular dysfunction
following myocardial infarction. This medication is prescribed to clinically
stable patients who have survived the acute phase of a myocardial infarction
and have a left ventricular ejection fraction of forty percent (with or without
symptomatic heart failure) (for more information, see clinical trials).
Hypertension: carvedilol is also indicated for the management of essential
hypertension. It can be used alone or in combination with other
antihypertensive agents, especially thiazide- type.
21. Contraindications/Cautions:
• hypersensitivity to drug/class/component.
• bradycardia, severe
• 2nd or 3rd degree AV block
• heart failure, uncompensated
• cardiogenic shock
• sick sinus syndrome w/o pacemaker
• asthma, bronchial
• hepatic diminishing
• avoid unexpected withdrawal
22. Warning and precaution:
The profile of adverse events observed with carvedilol phosphate was generally
comparable to that observed with the administration of immediate-release
carvedilol in clinical trials of COREG CR in patients with hypertension (338
subjects) and in patients with left ventricular dysfunction following a myocardial
infarction or heart failure (187 subjects). These patients were all experiencing
heart failure. As a result, the information that is presented in this section is
derived from the findings of controlled clinical studies that were conducted using
COREG CR and immediate-release carvedilol.
As a result, the information that is presented in this section is derived from the
findings of controlled clinical trials that were conducted with carvedilol and
immediate-release carvedilol. 48
23. 4. AIM AND ODJECTIVES
The aim of the thesis project was to optimize the preparation (wet media milling
technique) and characterization methods of nanosuspensions for poorly water-
soluble drug compounds, then formulate the nanosuspensions into suitable
pharmaceutical dosage forms, and finally test the efficacy in in vitro testing.
The more specific objectives of the present study are:
1. Optimization of Nanosuspension Preparation Parameters
2. Importance of Particle Size on Dissolution
3. "Nanos-in-Micros" Pharmaceutical Formulation
4. In Vitro Efficacy Testing
By studying critical process parameters, assessing the impact of particle size on
dissolution behavior, developing innovative pharmaceutical formulations, and
conducting in vivo efficacy tests, the project seeks to contribute to the
advancement of nanosuspension technology for enhanced drug delivery and
therapeutic outcomes.
24. AIM & OBJECTIVE
The aim of the research assignment was to enhance the preparation (wet media
milling technique) and characterization methods of nanosuspensions for poorly
water-soluble drug compounds, subsequently formulate the nanosuspensions into
appropriate pharmaceutical dosage forms, and ultimately evaluate the efficacy
through in vitro testing.
The more specific objectives of the present study are:
Importance of Particle Size on Dissolution:
The research seeks to examine the relationship between particle size and the
dissolving characteristics of nanosuspensions of weakly water-soluble drugs. Both
modeling and experimental techniques are utilized to ascertain distinguishing
dissolution conditions. This entails assessing the impact of varying particle sizes on
the rate and amount of drug dissolution, which is essential for enhancing drug
bioavailability.
25. In Vitro Efficacy Testing:
The research examines the efficacy of nanocrystal formulations in vitro for
medication release. The objective of this work is to employ nanotechnology to
develop nanoparticles that improve the solubility of weakly water-soluble drugs,
hence enhancing bioavailability. This stage is essential for assessing the practical
therapeutic potential of the improved nanosuspension formulations.
This thesis topic seeks to enhance the synthesis and characterisation of
nanosuspensions for poorly water-soluble pharmaceutical molecules. The project
aims to advance nanosuspension technology for improved drug delivery and
therapeutic outcomes by examining critical process parameters, evaluating the
influence of particle size on dissolution behavior, creating novel pharmaceutical
formulations, and performing in vivo efficacy assessments.
26. 1. Literature Review
2. Procurement of drug and excipients
3. Preformulation Studies
a) Determination of λmax of the drug
b) Calibration curve
c) Partition coefficient
d) Solubility Studies
4. Formulation development of Nanosuspension.
5. Evaluation of Nanosuspension
a) Particles Size
b) Size distribution
c) Vesicle size determination
d) In vitro drug release
6. Stability Studies
5. PLAN OF WORK
27. 6. METHODOLOGY
6.1 Preformulation studies:
Preformulation studies can be defined as investigation of physical & chemical
properties of drug substance alone and when combined with excipients.
Preformulation studies are the first step in rational development of dosage form of a
drug substance.
The objectives of Preformulation studies are to develop a portfolio of information
about the drug substance, so that this information is useful to develop a portfolio of
information Preformulation investigations are designed to information is useful to
develop formulation.
6.1.1 Solubility Studies:
a. Solubility study in water:
Drug was added in 100 mg in conical flasks containing 50 ml of distilled water. The
flasks were tightly corked and placed in a water bath at 37.0 ± 0.50 C agitated at 100
rpm for at least 12 hrs. Samples were taken at 12 hrs and filtered through 0.45 μm
filter, diluted with the medium and the drug concentration in the final sample
solutions was determined spectrophotometrically at. Each solubility value was
determined in triplicate and the results reported are the mean of the three.
28. b. Solubility study in buffer:
Drug was added in 100 mg in six conical flasks each containing pH 1.2
hydrochloric acid, pH 3.0 acid phthalate buffer, pH 4.5 acetate buffer and pH
5.8, 6.8 and 7.2 potassium phosphate buffers were prepared as per IP. The
buffers were prepared using distilled water. The solubility of drug in the
buffers was measured in the similar manner as in water.
6.1.2 Determination of UV absorption maxima (ƛmax) of drug:
The stock solution (100µg/ml) of carvedilol was prepared in pH 6.8 phosphate
buffer and diluted with 50 ml prepared stock solution. & to obtain
concentration of 10 µg/ml. The resultant solution was scanned in the range of
200 – 400 nm on double beam UV spectrophotometer against phosphate
buffer as a blank solution. Spectrum was recorded and the suitable absorption
maxima were selected at 241 nm.
30. Chemical / Material Source / Manufacture
Ethanol Absolute Changshu Yanguan Chemicals,China
Hydroxy propyl Methyl cellulose 15000 cps Central Drug House (P) Ltd. New Delhi, India
Lecithin VAV Life Scince Pvt ltd Mumbai India
Benzyl Alcohol Thomas baker (chemicals) Pvt. Ltd Mumbai, India
Tween 20 Central Drug House Delhi, India
Poloxamer Molychem. Pvt. ltd. Mumbai, India
PVP Loba Chemical Pvt. Ltd. Mumbai, India
DMF Qualigens Fine chemicals
Povidone Qualigens Fine chemicals
Tween-80 Thomas baker (chemicals)Pvt. Ltd Mumbai,India
Hexane Molychem. Pvt. ltd. Mumbai, India
Acetone Thomas baker (chemicals)Pvt. Ltd Mumbai,India
Table 6.2: Chemical used during the Experimental work
31. Equipment Manufacture
Bath sonicator Raj Analytical Services Mohali,India
Electronic weighing balance Shimadzu , Japan
Eppendorf tubes Tarsons Product Pvt.Ltd.,Kolkata,India
Hot air oven Narang Scientific Works New Delhi,India
Magnetic stirrer Remi scientific Instruments Mumbai
Membrane filters Advanced Micro Devices Ambala cantt,India
Microcentrifuge Remi scientific Instruments Mumbai,India
Vacuum pump Suguna single phase Chennai,India
Micropipette Accupipet Mumbai ,Indaia
Particle size Analyzer Malvern Mastersizer Instruments Ltd.,UK
pH meter Labindia Ltd.Mumbai,India
Prob Sonicator Mesonix,New York,USA
UV Spectrophotometer Shimadzu , Japan
Vials Tarsons Products Pvt.Ltd.,Kolkata,India
Vortex-type mixer Perfit India
Tissue Homoginizer Remi scientific Instruments Mumbai,India
Table 6.3: Equipment used during the Experimental work
32. 7. RESULTS AND DISCUSSION
Angle of repose 39.87
Bulk Density 0.63±0.04 gm/cm3
Tapped Density 0.77±0.02 gm/cm3
Compressibility (%) 18.18 %
Hausner’s ratio 1.22
7.1 Preformulation studies:
7.1.1 Micromeritical Study:
Table 7.1: Micrometrical Study of Carvedilol Drug
7.1.2 Solubility Study:
Carvedilol is a whitish powder it was soluble in methanol and Ethyl acetate.
Solubility in distilled water and buffer solutions:
The solubility of carvedilol in distilled water was found to be 2.60 μg/ml. Solubility at
different pH was in following order: pH 3.0 (380 μg/ml )> pH 4.5 (341 μg/ml) > pH
1.2(290 μg/ml) > pH 5.8 (133.11 μg/ml) > pH 6.8 (80.33 μg/ml) > pH 7.2 (72.11 μg/ml).
33. 7.1.3 Appearance:
Microparticles were small spherical shape particle, nonporous & uniform mixture.
7.2 Analytical Method development by UV Spectroscopy
7.2.1 Standard curve for Carvedilol
It refers to the ability of the analytical procedure to obtain results that are directly
proportional to the concentration of analytes at the target level. The linearity for
the Carvedilol spectrophotometric analysis was determined by performing a linear
regression analysis of the absorbance Carvedilol verses concentration plot
(standard curve).
The data of the standard curve is described by a linear equation.
Y=m x + c
35. 7.4.4 Stability of Carvedilol Nanosuspension
According to physiochemical analyses, including characteristics such as
particle size, PDI, drug content %, and in-vitro release tests, the Carvedilol
formulation (F2), made from a mixture of soya lecithin and TPGS, was selected
for expedited stability studies. The formulation at room temperature and at 40
°C exhibited a small increase in particle size. The in-vitro dissolution profile
data of the nano-formulation indicates that the solubility rates of Carvedilol
were adequate in 0.1N HCl. The residual medication content % was
exceptional after three months. The aforementioned facts are shown in Table
7.9.
Table.7.8: Particle size analysis of selected Carvedilol Nanosuspension (F2)
formulation
Formulation Storage
temperature
condition
Initial particle
size (nm)
Particle size after
three months (nm)
F2
Room temperature
81.75 ± 92.86
86.63 ± 94.67
400
C 92.13 ± 12.59
37. Summary and Conclusion
SUMMARY:
To produce the Nanosuspension formulation of Carvedilol, the preformulation
studies conducted for Carvedilol revealed key micromeritic properties indicative
of its flow characteristics and powder behavior. The angle of repose was found
to be 39.87°, suggesting fair to passable flow properties. The bulk density and
tapped density were recorded as 0.63 ± 0.04 g/cm³ and 0.77 ± 0.02 g/cm³,
respectively. These values indicate a moderate packing ability of the powder.
The compressibility index (Carr’s index) was calculated to be 18.18%, and the
Hausner’s ratio was 1.22, both of which further suggest fair flow properties.
These results provide a foundational understanding of Carvedilol’s physical
characteristics, which are essential for the development of a suitable and
efficient drug delivery system. Carvedilol shows significantly higher solubility in
organic solvents compared to water. It is most soluble in DMF
(131.41 ± 1.45 mg/mL) and benzyl alcohol (110.01 ± 1.64 mg/mL), followed by
ethanol (23.76 ± 1.45 mg/mL) and acetone (7.57 ± 0.54 mg/mL). In contrast, its
solubility in water is extremely low (0.03 ± 0.91 mg/mL), indicating poor
aqueous solubility and a strong preference for lipophilic environments.
38. CONCLUSION
In conclusion, Carvedilol nanosuspension formulations required extensive
characterization and optimization. Initial purity investigations showed Carvedilol
met pharmacopoeia criteria, allowing for further development. Carvedilol's 241
nm absorption maxima confirmed its structure using UV spectroscopy.
According to Beer-Lambert's law, calibration curves showed a linear connection
between Carvedilol concentration and UV absorbance. Stabilizers were
examined for particle size and dispersion to make nanosuspensions using high-
pressure homogenization. The nanosuspensions had homogeneous particle
sizes and limited size distributions, indicating stability and drug delivery
capability.
39. Formulation F2 was the optimal nanosuspension, with high drug content,
entrapment effectiveness, and simulated stomach fluid solubility. In-vitro
dissolution tests revealed zero-order F2 release kinetics, emphasizing
continuous and controlled drug release over 12 hours. Stability experiments
showed that the optimized formulation did not alter in physical appearance or
medication content after 90 days under accelerated settings. These findings
suggest that Carvedilol nanosuspensions may increase therapeutic efficacy by
improving stability, solubility, and controlled release. The successful creation of
Carvedilol nanosuspension formulation may improve medication solubility,
bioavailability, and therapeutic efficacy, enabling better treatment alternatives
for numerous medical problems.
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![3. DRUG PROFILE
Carvedilol:
Generic name:- carvedilol
Chemical formula: - C24
H26
N2
O4
Molecular weight: - 513.5 gm/mol.
Chemical name: (±)-[3-(9H-carbazol-4-yloxy)-2—hydroxypropyl]-[2-
(2methoxyphenoxy)ethyl]amine
Category: - Antihypertensive activity.
Half life: 7-10 hour
Dose: 3.125 to 25 mg. twice a day
Description: A white or almost crystalline powder
Solubility: sparingly soluble in water and soluble in methanol.
Melting point: 114-1150
c.
Bioavailability: 25% - 35%
Mechanism of Action: Carvedilol is a racemic mixture in which nonselective β-
adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic
blocking activity is present in both R(+) and S(-) enantiomers at equal potency.](https://image.slidesharecdn.com/newpuneetpptonformulationevalutionofnano-suspensionofcarvedilol-250622054452-9c3e8d65/85/new-Puneet-PPT-On-Formulation-Evalution-of-Nano-Suspension-of-Carvedilol-pptx-15-320.jpg)
