FORMULATION AND EVALUATION OF EXTENDED RELEASE MICROCAPSULES OF LAMIVUDINE
CHAPTER-4
MATERIALS AND
METHODS
|
Drug Name |
Source |
|
Lamivudine |
Alchem laboratories, Mumbai ,
India |
4.1.2 Excipients and chemicals used in the present study
4.1.3 List of Equipments used in the study
4.2 DOSAGE FORMS
SELECTED IN THE PRESENT STUDY
4.2.1 Single unit system (matrix tablets)
Matrix
drug delivery systems consist of a polymer, drug, and other excipients
distributed throughout the matrix. This system is dependent on polymer wetting,
polymer hydration, and polymer dissolution for the controlled release of drug.
At the same time, other soluble excipients or drug substances comprising the
tablet will also become wet, dissolve, and diffuse out of the matrix, while
insoluble excipients or drug substances will be held in place until the
surrounding polymer/excipient/drug complex erodes or dissolves away.
Figure 4.1
Schematic representation of drug release from the matrix tablets
4.2.2 Microparticles
These
are particles with size more than „1‟ m, containing the polymer. At
present, there is no universally accepted size range that particles must have
in order to be classified as microparticles. However, many workers classify the
particles smaller than „1‟ m, as nanoparticles and those more than 1000 m, as
macroparticles. Classification: Microparticles are classified into two groups
Microcapsules:
Microcapsules
are small particles that contain an active agent or core material surrounded by
a coating or shell. (Commercial microcapsules typically have a diameter between
3 & 800 micrometer and 10-90% core).
Microspheres:
Microspheres
are solid, spherical particles containing dispersed drug molecules, either in
solution or crystalline form, among the polymer molecules.
4.3
GENERAL METHODS IN THE PREPARATION AND CHARACTERIZATION OF MATRIX TABLETS AND
MICROCAPSULES
4.3.1 Preparation of Matrix Tablets using direct
compression method
The
drug, polymer(s) and all other excipients sifted through 425 μm sieve (ASTM
mesh no 40) and mixed uniformly. The dry mix blend was then pre lubricated with
respective excipients and lubricated with magnesium stearate. The lubricated
granules were directly compressed on 16-station tablet compression machine
using respective punches. (Cadmach Co, Ahmedabad, India).
4.3.2 Preparation of Matrix Tablets using Wet
granulation method
The
drug, polymer and other excipients were sifted through 425 μm sieve (ASTM mesh
no 40) and mixed uniformly. The dry mix blend was then granulated with
respective granulation fluid. The wet granules were dried at 60 °C until the
complete evaporation of granulation fluid from the granules. The dried granules
were again sifted through ASTM mesh no 30.
The
dried and sifted granules were then pre lubricated with respective excipients
and then lubricated with magnesium stearate. The lubricated granules were
compressed on 16-station tablet compression machine using respective punches.
(Cadmach Co, Ahmedabad, India).
4.3.3 Preparation of Microcapsules
Microcapsules
were prepared by using solvent evaporation method. The drug and polymer were
dissolved/dispersed in 25 ml of the organic solvent (Acetone). A 100 ml of
heavy liquid paraffin was taken in 250 ml beaker and kept for stirring at
750-800 rpm. The dispersed /dissolved drug –polymer solution was slowly added
to the heavy liquid paraffin under stirring condition. Stirring was continued
until the complete evaporation of the acetone from the liquid manufacturing
vehicle. The prepared microcapsules were filtered and washed with n-hexane to
remove the liquid paraffin and to harden the microcapsules. The micro capsules
were dried at 40 °C for the complete evaporation of the solvent. Fig 3.2
describes the process for the preparation of microcapsules.
4.3.4 Solubility determination of drugs
Solubility
study of the active drug was investigated in four different media as follows:
1) Purified water 2) 0.1 N hydrochloric Acid (HCl), USP 3) Acetate buffer pH
4.5, USP 4) Phosphate buffer pH 6.8 USP Required quantity of above media was
transferred in to a volumetric flask and heated up to 37 ±0.5 oC using magnetic
stirrer provided with heat. Previously weighed quantity of active drug was
added to the above volumetric flask until the saturation point occurs. The
total quantity of drug added was recorded. Stirring was continued up to 5 hours
at 37 ±0.5 oC. The sample was filtered through 0.45 μm filter. A measured
quantity of filtered sample was transferred in to another volumetric flask and
further dilutions made. The absorbance was measured using UV visible
spectrophotometer (Schimadzu, UV-1700 E 23).
4.3.5 Construction of standard calibration curves
Accurately
weighed quantity of active drug was transferred in to the volumetric flask.
Required quantity of media was added to the above volumetric flask. Shake the
volumetric flask until the complete solubility of the drug and make up the
volume with remaining quantity of media. Similarly stock solutions were
prepared in all the media. Standard calibration curves in different media were
constructed using the above stock solutions. The samples were scanned
formax at the UV range of 200-400 nm. After 1 day again the samples were
scanned for max. The max at initial and 1 day were compared for the stability
of pure drug in the respective media. From the above stock solutions different
concentrations of the solutions were prepared and standard calibration curves
were prepared by plotting the absorbance values vs concentration.
4.3.6 Fourier Transform Infrared spectroscopy
(FT-IR)
The
FT-IR spectrums of pure drug, initial formulation and stability samples of both
matrix tablets and microcapsules were determined. A FT-IR (Thermo Nicolet 670
spectrometer) was used for the analysis in the frequency range between 4000 and
400 cm-1, and 4 cm-1 resolution. The results were the means of 6
determinations. A quantity equivalent to 2 mg of pure drug was used for the
study
4.3.7 Differential scanning calorimetry (DSC)
Thermal properties of pure drug, initial formulation and stability
samples of both matrix tablets and microcapsules were evaluated by Differential
scanning calorimetry (DSC) using a Diamond DSC (Mettler Star SW 8.10).
The analysis was
performed at a rate 5 0 C min-1 from 500 C to 2000 C temperature range under
nitrogen flow of 25 ml min-1.
4.3.8 Drug content estimation
The
drug content of the prepared matrix was determined in triplicate. From each
batch, 20 tablets were taken, weighed, crushed and finely powdered. An
accurately weighed quantity of this powder was taken and suitably dissolved
under sonication (Power sonic 505, HWASHIN Technology Co.) in pH 6.8 phosphate
buffer and filtered through 0.45μ (Millipore) filters. The sample
was analyzed after making appropriate dilutions using the developed analytical
method.
4.3.9 Hardness, weight variation and friability
determination
The
weight variation was determined by taking 20 tablets using an electronic
balance (type ER182A, Mettler Toledo). Tablet hardness was determined for 10
tablets using a Monsanto tablet hardness tester (MHT-20, Campbell Electronics,
Mumbai, India). Friability was determined by testing 10 tablets in a friability
tester (FTA-20, Campbell Electronics) for 300 revolutions at 25 rpm.
4.3.10 In vitro drug release studies of prepared
matrix tablets and microcapsules
The
in vitro dissolution studies were performed up to 14 hours and more using
dissolution apparatus (LABINDIA, DISSO-2000, Mumbai, India). The dissolution
medium consisted of phosphate buffer pH 6.8 (900 mL), maintained at 37 ±0.5 °C.
An aliquot (5 mL) was withdrawn at specific time intervals and filtered through
0.45 μ (Millipore) filter.
After
appropriate dilution the samples were analyzed and cumulative percentage of the
drug released was calculated. 6 tablets from 3 different batches were used in
analysis.
4.3.11 Accelerated stability studies on the
prepared formations
Selected
formulations from prepared formulation were filled in HDPE containers and
stored at the following conditions like 40°C/75% RH for about 3 months as per
ICH guidelines. The samples were characterized for percent drug content, FTIR
and DSC study.
4.3.12 Kinetic analysis of dissolution data
The
release rate and mechanism of drug release from the prepared formulations were
analyzed by fitting the dissolution data into the zero-order equation Q = k0t
where Q is the amount of drug released at time t, and k0 is the release rate constant,
The dissolution data was fitted to the first order equation ln (100–Q) = ln 100
– k1t. where k1 is the release rate constant. The dissolution data was fitted
to the Higuchi‟s
equation Q = k2 t1/2
4.3.13 Statistical Comparison of Dissolution
Profiles
Dissolution
studies of the prepared matrix tablets and microcapsules for all the
formulations were determined. A statistical comparison such as similarity
factor (f2 factor) among some formulations was used. This statistical model is
suitable only when three or more dissolution time points are available. The
similarity factor (f2) is a logarithmic reciprocal square root transformation
of the sum of squared error and is a measurement of the similarity between two
curves in the dissolution. The following equation represents a similarity
factor (f2):
where 1) f2 similarity factor, log is logarithm
to base 10, 2) P is number of sampling time points, 3) Σ is the summation of
over all time points, 4) μti is the dissolution measurement (in mean percent
labeled amount) at time point “t” of the first batch (test batch) profile, 5)
μri is the dissolution measurement (in mean percent labeled amount) at time
point t of the second batch (reference batch) profile.
4.3.14 Encapsulation efficiency (EE)
Drug
loaded microcapsules (100 mg) were powdered and suspended in water. Then the
contents suspended in the water were kept for sonication (Power sonic 505,
HWASHIN Technology Co) for about 20 mins and shaked using mechanical shaker
(ORBITEX, Scigenics Biotech) for about 20 mins for the complete extraction of
drug from the microcapsules. The resultant solution was filtered through 0.45
μm filter. Drug content was determined by UV- visible spectrophotometer
(Schimadzu, UV-1700 E 23).
The percent entrapment was calculated by using
the following formula.
4.3.15 Particle size distribution of
microcapsules and granules
Particle
size analysis99 of the microcapsules was done by sieving method using Indian
Standard Sieves (Test Sieves ASTM-E-11) #10, #20, #30, #40, #60 and #80, #100,
#120 fitted to a mechanical vibrator-shaker. The fractions were calculated by
collecting for each sieve and percent retained and cumulated percent retained
were calculated.
4.3.16 Scanning electron microscopy (SEM)
Morphological
characterization of the microcapsules was done by using Scanning electron
microscope (JEOL JSM -5200). The samples were coated to 200 A° thickness with
gold-palladium prior to microscopy.
Pre formulation studies
Determination of Lamivudine solubility
Solubility
study of LAMI in different media was determined by the general procedure
described.
Construction of standard calibration curves for
LAMI
Standard
graph of LAMI was determined by the general procedure described.
Multimedia dissolution of marketed lamivudine
formulation
The
drug release rate from lamivudine marketed conventional tablets (Epivir-150 mg,
Batch No-B134293, manufactured by Glaxo smithkline) was characterized using USP
type 2 at 50 rpm, using 900 ml of dissolution medium at 37 ±0.5 °C. The various
dissolution media used in the study were water, 0.1 N HCl, USP acetate buffer
pH 4.5 and USP phosphate buffer pH 6.8. A sample of 5 ml was withdrawn from the
dissolution medium and replaced with 5 ml of blank media. The samples were
withdrawn at 5, 10, 15, 30 and 45 minutes and analyzed using UV visible
spectrophotometer after suitable dilution.
Fourier Transform Infrared spectroscopy (FT-IR)
The
FT-IR spectrum was taken for pure LAMI powder, initial formulation and
stability samples were determined by the method described.
Differential scanning calorimetry (DSC)
Thermal
properties of pure LAMI powder, Initial formulation and stability samples were
evaluated by the method described.
Analytical Methods Ultraviolet Spectroscopy
The UV
spectroscopic method for LAMI was developed in the four different pH media to
study the solubility, dissolution and drug content estimation in the prepared
formulations was determined by the method described. The quantity of LAMI was
calculated from the regression equation of the calibration curve.
Formulation of Lamivudine matrix tablets
Matrix
tablets of LAMI were prepared using various proportions of HPMC and combination
of HPMC and PEO as the retarding polymer. The tablets were manufactured by the
direct compression procedure described. The lubricated granules were directly
compressed using 9 mm flat faced round (FFR) punch. Fig 4.1 describes the
process for the preparation of matrix tablets. Three batches were prepared for
each formulation and compressed 500 tablets from each batch for the characterization
study. The formulae and physical characteristics of the prepared matrix tablets
are given in Table 4.5.
Characterization of the Designed Tablets Drug content
estimation
The
drug content of the prepared matrix tablets was determined by the general
procedure described. The sample was analyzed after making appropriate dilutions
using the developed analytical method.
Hardness, weight variation and friability determination
The weight variation, hardness and friability were determined by
the general procedure described in the section.
Moisture uptake study of tablets and granules
Moisture
uptake study on the granules and tablets was carried out at different relative
humidity (RH) conditions100 like 33%, 54% and 90% RH for assigning
environmental conditions during the manufacture process and storage. The
humidity conditions were maintained by preparing the saturated solution
of magnesium chloride for 33% RH, saturated solution of sodium dichromate for
54% RH and saturated solution of potassium nitrate for 90% RH. Then these
solutions were transferred separately into three desiccators and allowing them
for 24 hours to get saturation inside the desiccators. Then accurately weighed
granules and tablets prepared with HPMC and combination of HPMC and PEO were
spread in Petri dishes and kept in seperate desiccators. The samples were
weighed at 24, 48, 72, 96 and 120 hrs and the percent moisture uptake was determined.
In vitro drug release studies
The in vitro
dissolution studies were performed using USP type I dissolution apparatus
(LABINDIA, DISSO-2000, Mumbai, India) at 100 rpm. The dissolution medium
consisted of phosphate buffer pH 6.8 (900 ml), maintained at 37°C ±0.5 °C. An
aliquot (5 ml) was withdrawn at specific time intervals and filtered through
0.45 μ (Millipore) filter. After appropriate dilution the samples were analyzed
and cumulative percentage of the drug released was calculated. 6 tablets from 3
different batches were used in data analysis.
Effect of tablet SA and SA/Vol on drug release from HPMC matrix
tablets
Selected
formulations based on the in vitro dissolution study were compressed with
different size round flat faced punches. Tablet surface area (SA) and volume
(Vol) were determined for each tablet by measuring tablet band thickness. The
measured tablet thickness was used in tooling specific equations to calculate
the tablet surface area and volume. The following equations were used to
calculate the surface area and volume for the flat faced round tablets (46).
SA = 2
π r (r + t) -------------------------- (1)
SA/Vol
= 2 (r + t) / r t -------------------------- (2)
Where r is the radius of the tablet and t is the
band thickness of the tablet. The matrix tablets prepared with HPMC K 100 M
were used in this study.
Accelerated stability studies on the prepared
formulations
Selected
formulations (F-2 and F-5) from prepared matrix tablets were filled in HDPE
containers and stored at the following conditions like 40°C/75% RH for about 3
months as per ICH guidelines. The samples were characterized for % drug content
and FTIR study.
Statistical Comparison of Dissolution Profiles
Dissolution
profiles were constructed and the similarity factor (f2 factor) was used to
compare the dissolution profile of different formulations and also with the
stability samples by the method described.
Drug Profiles
Zidovudine
(AZT) 86
First anti retroviral drug
approved by USFDA-March 1987
Structural formula of zidovudine
Physicochemical
properties of Zidovudine
|
|
Description |
A White to
yellowish, odorless, crystalline solid |
|
|
CAS No2 |
30516-87-1 |
Molecular Formula C10H13N5O4
|
|
Molecular Weight |
267.24. |
|
|
Chemical Name |
3'-azido-3'-deoxythymidine |
|
|
Melting Range |
About 124°C |
|
|
Solubility |
soluble in
water, soluble in ethanol |
Mechanism of Action:
Zidovudine
is a synthetic nucleoside analogue of the naturally occurring nucleoside,
thymidine, in which the 3′-hydroxy (-OH) group is replaced by an azido (-N3)
group. Zidovudine is converted to its active metabolite, zidovudine
5′-triphosphate (AztTP), with the action of the cellular enzymes. Zidovudine
5′-triphosphate inhibits the activity of the HIV reverse transcriptase both by
competing for utilization with the natural substrate, deoxythymidine
5′-triphosphate (dTTP), and by its incorporation into viral DNA. The active
metabolite AztTP is also a weak inhibitor of the cellular DNA polymerase-alpha
and mitochondrial polymerase-gamma and has been reported to be incorporated
into the DNA of cells in culture.
Antiviral Activity:
The in vitro anti-HIV activity of
zidovudine was assessed by infecting cell lines of lymphoblastic and monocytic
origin and peripheral blood lymphocytes with laboratory and clinical isolates
of HIV. The IC50 and IC90 values (50% and 90% inhibitory concentrations) were
0.003 to 0.013 and 0.03 to 0.13 mcg/mL, respectively (1 nM = 0.27 ng/mL).The
IC50 and IC90 values of HIV isolates recovered from 18 untreated AIDS/ARC
patients were in the range of 0.003 to 0.013 mcg/mL and 0.03 to0.3 mcg/mL,
respectively.
Pharmacokinetics of zidovudine
1.
Absorption
Rapidly absorbed and extensively distribute, The extent of Zidovudine
absorption (AUC) was similar when a single dose of Zidovudine was administered
with food.
2.
Distribution
Volume of distribution (Vd) oral 1.6
± 0.6 L/kg. Protein binding: <38.
Pharmacokinetics
of Zidovudine was dose independent at oral dosing regimens
ranging from 2 mg/kg every 8 hours to 10 mg/kg every 4 hours
3.
Metabolism
Zidovudine is primarily eliminated by hepatic metabolism. The metabolite of
Zidovudine is 3'-azido-3'-deoxy-5'- O - (beta)- D -glucopyranuronosylthymidine
(GZDV). Another metabolite is 3'-amino-3'-deoxythymidine (AMT).
4.
ExcretionElimination half-life: 0.5 to 3 hours
|
|
The systemic clearance is 1.6 ± 0.6 L/hr/kg. |
||
|
|
Eliminated
via the kidneys; Urinary
recovery of zidovudine |
||
|
|
and
GZDV accounts for 14% and 74%, respectively, of the |
||
|
|
dose
following oral administration. |
||
|
5. Pharmacoki |
Parameter |
|
Value |
|
netic |
Peak |
plasma |
41.8 ± 7.7 ng/mL following 15 |
|
Parameters |
concentration |
|
mg oral dose |
|
|
T max |
|
About 2 hours (0.25 - 2.0) |
|
|
Elimination Half-life |
0.5 to 3 hours |
|
|
|
Volume of distribution |
4.5 ± 1.7 liters |
|
Polymers
Hydroxy
propyl methyl cellulose (HPMC)
R is H, CH3,
or CH3CH(OH)CH2
Structural formula
Functional Category: Coating agent; extended release
agent
Applications: Tablet binder, in film-coating,
and as a matrix for use in
extended-release tablet formulations.
Description: Hypromellose is an odorless and
tasteless, white or creamy-white
fibrous or granular powder Glass
transition temperature: 170–180°C.
Melting point: 190–200°C.
Solubility:
Soluble in cold water, forming a
viscous colloidal solution; practically
insoluble in chloroform, ethanol (95%), and ether, but soluble in mixtures of
ethanol and dichloromethane, mixtures of methanol and dichloromethane, and
mixtures of water and alcohol. Few grades of HPMC are soluble in acetone,
mixtures of dichloromethane and propanol, and other solvents.
Viscosity: Wide range viscosity grades are
available in the market.
Stability and Storage Conditions: Hypromellose powder is a stable material, although it is hygroscopic
after drying.
Ethyl cellulose (EC) 90
Structural formula
Functional
Category: Ethyl
cellulose (EC) is used as an enteric film
coating material, or as a matrix binder for tablets and capsules and also
as tablet diluent.
Applications: binders, fillers, granulation
aids, protective and controlled
release coatings, taste masks and flavor fixatives.
Description: It is a white, tasteless, free
flowing powder.
Glass transition temperature: 129-133°C
Melting point: 165-173°C.
Solubility:
Practically insoluble in water,
freely soluble in chloroform, soluble
in dichloromethane.
Viscosity: Various grades of ethyl
cellulose are commercially available having
viscosities ranging from 3-385 mPa s.
Stability and Storage Conditions: cellulose acetate butyrate is
stable if stored in a well-closed
container in a cool, dry place
Lubricants
Magnesium stearate [79]
|
Non-proprietary
names |
: |
Magnesium stearate
(BP, USP) |
|
|
|
Magnesii
stearas (PhEur) |
Synonym : Dibasic
magnesium stearate, Magnesium distearate
|
Chemical Name |
: |
Octadecanoic acid magnesium salt |
|
Empirical Formula |
: |
C36H70MgO4 |
|
Molecular Weight |
: |
591.34 g/mol |
|
Functional Category |
: |
Tablet and capsule lubricant |
Description: It is a very fine, light white, precipitated or milled powder
of low bulk density, having a faint
odor of stearic acid and a characteristic taste. The powder is greasy to the
touch and readily adheres to the skin.
Physicochemical Properties
|
Density
(bulk) |
: |
0.159 g/cm3 |
|
(tapped) |
: |
0.286 g/cm3 |
|
(true) |
: |
1.092 g/cm3 |
|
Flowability |
: |
poorly flowing, cohesive
powder. |
|
Melting range |
: |
117–150°C (commercial samples) |
|
|
|
126–130°C (high purity magnesium stearate) |
|
Solubility |
: |
Practically insoluble in
ethanol (95%), ether and |
|
|
|
water; slightly soluble in
warm benzene and |
|
|
|
warm ethanol (95%). |
Stability and Storage :
Magnesium stearate is stable and should be stored in a well closed container in a cool, dry place.
Standards : Magnesium stearate contains not less than 3.8%
and not more than 5.0% of magnesium, calculated on the dried
basis.
Identification : To
5gm add 50 ml of ether, 20 ml of 2 M nitric acid and 20 ml of distilled water and heat under a
reflux condenser until fully dissolved. Allow to cool. Separate the aqueous
layer and shake the ether layer with two quantities (each 4 ml) of distilled
water. Combine the aqueous layers, wash with 15 ml of ether and dilute to 50 ml
with distilled water. Evaporate the ether layer and dry the residue at 105˚ C.
The freezing point of the residue is not lower than 53˚ C.
Assay : Weigh accurately about
0.75 gm, add 50 ml of a mixture of 1-butanol and ethanol, 5 ml of strong ammonia solution, 3 ml of ammonia buffer
pH 10.0, 30 ml of 0.1M disodium edetate and 15 mg of mordant black mixtures.
Heat to 45˚ to 50˚ C and titrate with 0.1 M zinc sulphate until the colour
changes from blue to violet. Repeat the operation. The difference between the
titrations represent the amount of disodium edentate. Each ml of disodium
edetate is equivalent to 0.002431 gm of Magnesium.
Applications: It is
widely used in cosmetics, foods, and pharmaceutical formulations. It is primarily used as a lubricant in
capsule and tablet manufacture at concentrations
between 0.25% and 5.0% w/w. It is also used in
barrier creams
Diluents
Micro
crystalline cellulose
|
Nonproprietary
Names |
: |
Microcrystalline
cellulose (BP), |
|
|
|
Cellulosum
microcristallinum (PhEur) |
|
Synonyms |
: |
Avicel pH, cellulose gel, crystalline cellulose |
|
Chemical
name |
: |
Cellulose |
|
Empirical
Formula |
:(C6H10O5)n,
where n = 220. |
|
|
Molecular
Weight |
: |
370.351
g/mol |
Description : It is
a purified, partially depolymerized cellulose that occurs as a white, odorless, tasteless, crystalline
powder composed of porous particles. It is commercially available in different
particle sizes and moisture grades that have different properties and
applications.
Structural
formula :
|
Density
(Bulk) |
: |
0.337
g/cm3 |
|
Density
(Tapped) |
: |
0.478
g/cm3 |
|
Density
(True) |
: |
1.512-1.668 g/cm3 |
|
Loss
on drying |
: |
≤
7.0% |
|
Melting
Point |
: |
chars at 260-270˚C |
|
Ash
value |
: |
0.1% |
|
Moisture
content |
: |
less
than 5% w/w |
Functional category : Adsorbent,
suspending agent, tablet and capsule diluent and tablet disintegrant.
Solubility :
Slightly soluble in 5% w/v sodium hydroxide solution. Practically insoluble in water, dilute acids and most
organic solvents.
Stability
:
Though it is a hygroscopic material, it is stable.
Storage
:
To be stored in a well closed container in a cool, dry place.
Lactose
Synonyms : Aero flow , fast flow, flowlac, milk
sugar,
Funtional
category: Tablet and capsule
diluents and channeling agrnt.
Description
:
White to off- white crystalline particles or powder.Lactose is odourless and slightly
sweet taste.
Physical
properties
Solubility
:
Highly soluble in water practically insoluble in chloroform , ethanol and ether
Bulk
density : 0.62 g/cm3
Tapped
density : 0.94 g/cm3
True
density :1.522 g/cm3
Specific
rotation :+52° to +52.6°
Stability
and storage Conditions:
Lactose may develop a brown coloration on storage, the
reaction being accelerated by warm damp conditions. Lactose should be storage
in a well-closed container in a cool, dry place.
Incompatibilities:
A
Maillard-type condensation reaction is likely to occur between lactose and
compounds with a primary amine group to form brown, or yellow-brown-colored
products.
Applications
in pharmaceutical technology:
Lactose
is widely used as filler diluents in tablets, capsule and to a more limited in
lyophilized products and infant-feed formulas.Direct compression grades are
generally composed of spray-dried lactose, which containts specially prepared
pure α-lactose monohydrate along with a small amount of amorphous lactose.
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