ISSN 2249-3875

International Journal of Pharmaceutical Erudition

Review Article
Basic Aspects of Process Validation of Solid Oral Dosage Forms

Sharma Tejal
Department of Pharmaceutics, B. N. Girls College of Pharmacy, Udaipur (Raj.)
313002(India)
Validation of the manufacturing process is performed in order to ensure that the
manufacturing process does what it purported to do. Pharmaceutical validation guarantees the
reliability and reproducibility of the manufacturing process. Validation is the collection and
evaluation of data, from the process design stage throughout production, which establishes
scientific evidence that a process is capable of consistently delivering quality products.
Process validation should normally be completed prior to the distribution and sale of the
medicinal product (prospective validation), if it is not possible, it may be necessary to
validate processes during routine production(concurrent validation) and processes in use
some time should also be validated(retrospective validation).this article examines the need for
pharmaceutical validation, the various approaches, processing stage and control variables
and sampling plan related to tablets dosage form.
Key word: Validation, Process validation, Control variables, tablets dosage form,
reproducibility

INTRODUCTION
The documented act of demonstrating that and the evaluation of data, from the
any process and activity will consistently process design stage throughout
lead to the expected results. It also production, which establishes scientific
includes the qualification of systems and evidence that a process is capable of
1
equipment . Manufacturer should plan consistently delivering quality products.
validation in a manner that will ensure
European Commission (EC):4
regulatory compliance and ensuring that
Validation is defined as “Action providing
the product quality, safety and consistency
in accordance with principles of GMP
are not compromised.2 Validation itself
(Good Manufacturing Practice), that any
does not improve processes but confirms
procedure, process, equipment, material,
that the processes have been properly
activity or system actually lead to the
developed and are under control. Different
expected results”.
agencies defined the validation as follows:
FDA:3 World Health Organization (WHO):5
Validation is defined as “The collection Validation is defined as “Action providing
*Address for correspondence that any procedure, process, equipment,
[email protected]

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material, activity or system actually lead to evaluated on the basis of experience or

the expected results”. theoretical considerations to determine the
Importance of Validation 6 critical parameters that may affect the
First, and certainly foremost, among the quality of the finished product. Minimum
reasons for validation is that it is a three consecutive batches of the product
regulatory requirement for virtually every shall be considered for the prospective
process in the global health care industry- validation study. This type of validation
for pharmaceuticals, biologics, and activity is normally completed prior to the
medical devices. Regulatory agencies distribution and scale of the drug product.
across the world expect firms to validate It is generally considered acceptable that
their processes. The continuing trend three consecutive batches/runs within the
toward harmonization of requirements will finally agreed parameters, giving product
eventually result in a common level of of the desired quality would constitute a
expectation for validations worldwide. proper validation of the process. It is
Utility for validation beyond compliance is preferred that the validation batches made
certainly available. The emphasis placed should be of the same size as the intended
on compliance as a rationale has reduced production scale batches.
the visibility of the other advantages a firm Concurrent Validation:
gleans from having a sound validation Establishing documented evidence that a
program. facility and processes do what they purport
to do, based on information generated
Benefits of Validation
during actual imputation of the process.
 Quality
This approach involves monitoring of
 Customer – patient satisfaction.
critical processing steps and end product
 It has been built into the product.
testing of current production, to show that
Types of Process Validation7
the manufacturing process is in a state of
Prospective Validation: control.
In Prospective Validation, the validation Retrospective Validation:
protocol is executed before the process is This type of validation is acceptable only
put into commercial use. During the for well-established processes, without any
product development phase the production change in the composition of the product,
process should be broken down into operating procedure and equipments. The
individual steps. Each step should be sours of data for these type of validation

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may include batch documents process regulations. Where deviations from device
control charts, maintenance logbook, specification could occur as result of
process capability studies, finished product manufacturing process itself. There shall
data, including trend data, and stability be written procedures describing any
data. process controls necessary to assure
conformance to specifications.
Revalidation:
Re-validation provides the evidence that
changes in a process and /or the process
environment that are introduced do not
adversely affect process characteristics and
product quality. Documentation
requirements will be the same as for the
initial validation of the process.

Government regulations
Validation is considered to be integral part
of GMPs essentially worldwide, Figure 1: Phases in Process validation
compliances with validation requirements
How validation is done
is necessary for obtaining approval to
The principle is characterized by harmony
manufacture and to introduce new
between the results obtained and
products. The FDA’s cGMP refer to the
requirements. This supposes Specific
concepts of the validation in both sections.
requirements and objectives
They state that such control procedure
 Available means
shall be established to monitor out put and
 Choices, which are justified in
to validate the performance of those
relation to objectives
manufacturing process that may be
 Each stage should begin when the
responsible for causing variability in the
 previous stage is over
characteristics of in process materials and
Certain depositions should be defined
drug materials. The Accuracy, sensitivity,
 How norms should be dealt with
specificity and reproducibility of test
 How modifications should be dealt
methods employed by the firm shall be
with controlling evaluation will
established and documented. A generally
involve
stated requirement for process validation is
contained in the medicinal device GMP  Set data for decision making

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 Evaluation before decision making 1. The use of different lots of raw

 Justifying the decision materials should be included. i.e., active
 Follow-up. drug substance and major excipients.
Table 1: Check list of Validation and 2. Batches should be run in succession and
Control Documentation
on different days and shifts (the latter
Sr. Selection of cGMP Validation and
No control condition, if appropriate).
. documentation
1 Introduction Establishing of QA
3. Batches should be manufactured in the
& PV functions equipment and facilities designated for
2 Organization and Establishment and
personnel facility installation eventual commercial production.
and qualification
3 Buildings and Plant and facility 4. Critical process variables should be set
facilities installation
qualification within their operating ranges and should
Maintenance and
not exceed their upper and lower control
sanitation
Microbial and pest limits during process operation. Output
control
4 Equipment Installation and responses should be well within finished
qualification
cleaning methods product specifications.
5 Air and water Water treatment
quality and steam systems
5. Failure to meet the requirements of the
air, heat and validation protocol with respect to process
vacuum handling
6 Control of raw Incoming input and output control should be
material, in-process components
material, Manufacturing non- subjected to process requalification and
product sterile products
7 Production and Process control subsequent revalidation following a
process controls systems
thorough analysis of process data and
(instruments and
computers) formal discussion by the validation team.
8 Packing and labeling Depyrogenation,
controls sterile packing, Protocol for Process Validation9
filling and closing.
9 Holding and Facilities Protocols should specify the following in
distribution
10 Laboratory controls Analytical methods detail:
11 Records and reports Computer systems a) A clear and precise definition of
12 Returned and Batch processing
salvage drug process equipment system or
products
subsystem, which is to be the subject
Strategy for Industrial Process
Validation of Solid Dosage Forms.7, 8 of study with details of performance
The strategy selected for process characteristics;
validation should be simple and b) Installation and qualification
straightforward. The following five points requirement for new equipment;
gives strategy for process validation: c) Any upgrading requirement for

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existing equipment with justification individuals against protocol criteria and

for the change(s) and statement of judged as meeting or failing the
qualification requirement; requirements. Written evidence supporting
d) Detailed stepwise statement of actions the evaluation and conclusion should be
to be taken in performing the study available. If such an evaluation shows that
(or studies); protocol criteria have not been met, the
e) Assignment of responsibility for study should be considered as having
performing the study; failed to demonstrate acceptability and the
f) Statement on all test methodology to reasons should be investigated and
be employed with a precise statement documented. Any failure to follow the
of the test equipment and/or materials procedure as laid down in the protocol
to be used; must be considered as potentially
g) Test equipment calibration compromising the validity of the study
requirements; itself and requires critical evaluation of all
h) References to any relevant standard the impact on the study.
operating procedures (SOP); Table 2: Protocol for title page in industry

i) Requirement for the current format of Name of the company

Process validation protocol
the report on the study; Product: Page No. : 1 of Page No.: 1
j) Acceptance criteria against which the ……. of …….
success (or otherwise) of the study is Protocol No. : Version No. :

to be evaluated; and Product name :

Label claim :
k) The personnel responsible for
Master Formula Record
evaluating and certifying the
(MFR) No. :
acceptability of each stage in the Batch Manufacturing Record
study and for the final evaluation and (BMR) No. :

certification of the process as a whole, Effective Date :

as measured against the pre-defined The final certification of the validation

criteria. study should specify the pre-determined
All personnel involved in conducting the acceptance criteria against which success
studies should be properly trained and or failure was evaluated.
qualified. All information or data Industrial Process Evaluation 8, 10, 11, 12
generated as a result of the study protocol Determine the unit operations needed to
should be evaluated by qualified manufacture the tablets.

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Table 3: Protocol approval blending technique and speed. If the

Prepared Checked By Approved
By
materials can be overmixed, resulting in
By
Signature demixing or segregation of the materials.
Date Demixing can occur due to the physical
Name
property differences (e.g., particle size
distribution and density).
Development(R&D)
(QA)/Research and

Control
Quality assurance

Drug uniformity: Content uniformity is

Department

Head – QA
Production

Quality usually performed to determine the

R&D

uniformity of drug throughout the mix or

blend. Representative samples should be
1. Mixing or Blending taken throughout the mix or blend. The
Materials that have similar physical sampling technique and handling of the
properties will be easier to form a uniform materials are key in obtaining valid
mix or blend and will not segregate as content uniformity results. Segregation of
readily as materials with large differences. the sample can occur by over-handling,
Mixing or blending technique: Diffusion resulting in inaccurate results. For the final
(tumble), convection (planetary or high blend (blend prior to compression), the
intensity), or pneumatic (fluid bed) sample taken should be equivalent to the
techniques can be used to mix or blend weight of a single tablet.
materials. Determine the technique that is Excipient uniformity: Besides drug
required for the formulation or process uniformity, excipients need to be uniform
objective. It may be different. in the granulation or blend. Two key
Mixing or blending speed: Determine the excipients are:
intensity (low/high shear) and/or speed i. Lubricant: The lubricant needs to
(low/high/optimal shear) (rpm) of the be distributed uniformly in the
mixing or blending. Mixing the drug and mixture/granulation for the high-speed
excipient will require more intense mixing compression operation. Uneven
than adding the lubricant to the final blend. distribution of the lubricant can result in
Mixing or blending time: How much picking and sticky problems during
mixing or blending is required to obtain a compression. It can also lead to tablet low
uniform mixture? The mixing or blending dissolution due to excessive lubricant in
time will be dependent on the mixing or some tablets.

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2. Wet Granulation
What type of wet granulation technique
will be used? Will it be low shear (e.g.,
Hobart), high shear (e.g., Diosna, GEI-
Collette) or fluid bed (e.g., Glatt, Fluid
Air)? Each technique will produce
granules with different physical properties
and will require monitoring of different

Figure 2: Schematic diagram of processing parameters.

processing steps and respective in-
process variables during tablet Binder addition: Should the binder be
manufacture added as a granulating solution or dry like
ii. Color: The colorant(s) need(s) to the other excipients? Adding the binder
be evenly distributed in the mixture so that dry avoids the need to determine the
the tablets have a uniform appearance optimal binder concentration and a
(e.g., color, hue, and intensity). The separate manufacture for the binder
coloring agent may need to be prescreened solution.
or more uniformly dispersed in the blend Binder concentration: The optimal
prior to compression to avoid speckling or binder concentration will need to be
shading of the color. determined for the formulation. If the
Equipment capacity/load: The bulk binder is to be sprayed, the binder solution
density of materials or granules will affect needs to be dilute enough so that it can be
the capacity of the equipment. If an pumped through the spray nozzle. It
excipient in the formulation affects the should also be sufficiently concentrated to
density of the final blend to a greater form granules without over wetting the
extent than any other ingredient, then a materials.
well-controlled density specification for Amount of binder solution/granulating
that excipient may be warranted. Test solvent: How much binder or solvent
different-sized loads in the mixer/blender solution is required to granulate the
(e.g., 30, 50, and 70% of working volume) material? Too much binder or solvent
for optimal mixing or blending. solution will over wet the materials and
Undercharging or overcharging a blender prolong the drying time. The amount of
can result in poor drug or tablet lubricant binder solution is related to the binder
distribution. concentration.

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Binder solution/granulating solvent Equipment size and capacity: The mill

addition rate: should be large enough to delump the
entire batch within a reasonable time
Define the rate or rate range at which
period to minimize manufacturing time
the binder solution or granulating solvent
and prevent the material from drying
can be added to the materials. Can the
during this operation.
granulating solution be dumped into the
mixer or does it have to be metered in at a Screen size: The screen needs to be small
specific rate? enough to delump the material, but not too
small to cause excessive heating of the
Mixing time:
mill, resulting in drying of the granulation.
How long should the material be mixed to
ensure proper formation of granules? Mill speed: The speed should be sufficient
Should additional mixing be required? to efficiently delump the material without
Granulations that are not mixed long straining the equipment.
enough can form incomplete or weak Feed rate: The feed rate of the wet
granules. These granules may have poor granulation is interrelated to screen size
flow and compression properties. On the and mill size and speed.
other hand, over mixing the granulation
4. Drying
can lead to harder granules and a lower
The type of drying technique (e.g., tray,
dissolution rate.
fluid bed, and microwave) required for the
Granulation end point: formulation needs to be determined and
How is the granulation end point justified. The type of technique may be
determined? Is it determined or controlled dependent on such factors as drug or
by granulation end point equipment (e.g., formulation properties and equipment
ammeter or wattmeter)? availability. Changing dryer techniques
could affect such tablet properties as
3. Wet Milling
hardness, disintegration, dissolution, and
Does the wet granulation need to be milled
stability. The optimal moisture content of
to break up the lumps and enhance drying
the dried granulation needs to be
of the granulation? Wet granules that have
determined. High moisture content can
a wide aggregate range can lead to
result in
inefficient drying (long drying times and
(1) Tablet picking or sticking
partially dried large granules or lumps).

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(2) Poor chemical stability as a result of needs to be known. A larger load will
hydrolysis. require more moisture to be removed on
An over dried granulation could result in drying and will affect the drying time. In
poor hardness and friability. Moisture the case of fluid bed drying, a maximum
content analysis can he performed using dryer load is that load above which the
the conventional loss-on-drying techniques dryer will not fluidize the material.
or such state-of-the-art techniques as near
5. Milling
infrared (NIR) spectroscopy. The milling operation will reduce the
Inlet/outlet temperature: The inlet particle size of the dried granulation. The
temperature is the temperature of the resultant particle size distribution will
incoming air to the dryer, while the outlet affect such material properties as flow,
temperature is the temperature leaving the compressibility, disintegration, and
unit. The inlet temperature is critical to the dissolution. An optimal particle size/size
drying efficiency of the granulation and distribution for the formulation will need
should be set high enough to maximize to be determined. Factors to consider in
drying without affecting the milling are:
chemical/physical stability of the
Mill type
granulation. The outlet temperature is an Screen size: A smaller screen size will
indicator of the granulation temperature produce a smaller particle size and a
and will increase toward the inlet greater number of fines.
temperature as the moisture content of the
Mill speed: A higher mill speed will result
granulation decreases (evaporization rate).
in a smaller particle size and possibly a
Airflow: There should be sufficient wider particle size distribution. It can also
airflow to ensure removal of moisture generate more heat to the product,
laden air from the wet granulation. depending on the screen size and feed rate,
Insufficient airflow could prolong drying which could affect the stability of the
and affect the chemical stability of the product.
drug. Airflow and the inlet/outlet
6. Lubrication
temperature are interrelated parameters
Amount of lubricant added: How much
and should be considered together.
lubricant is required? Too much lubricant
Equipment capability/capacity: The load will form hydrophobic layer on the tablet
that can be efficiently dried within the unit resulting in dissolution problems.

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Mixing time: How long should the materials being compressed will need to
material is mixed to ensure proper have adequate flow and compression
formation? Should mixing stop after the properties. The material should readily
addition of the lubricant or should flow from the hopper onto the feed frame
additional mixing be required? If not and into the dies. Inadequate flow can
mixed long enough form problems like result in “rat holing” in the hopper and/or
chipping, capping, etc. segregation of the blend in the hopper/feed
Table 4: Table of contents frame. This can cause tablet weight and
S. Title Page content uniformity problems. As for the
No. No.
1 Protocol Approval Sheet compressibility properties of the
2 Table of contents
3 Objective formulation, it should be examined on an
4 Scope
instrumented tablet press. Factors to
5 Validation term and responsibility
6 Steps for validation and consider during compression are as
acceptance criteria
7 Process flow chart follows:
8 Procedure
9 Form–A : Review of raw
material/packing material Tooling: The shape, size, and concavity of
10 Form–B : Evaluation of active raw
the tooling should be examined based on
material
11 Form–C : Evaluation of inactive the formulation properties and commercial
raw material
12 Form–D : Qualification of specifications. For intagliated (embossed)
equipment
13 Form–E : Test instrument tablets, factors such as the position of the
calibration
14 Form–F : Dry mixing
intagliation on the tablet and the
15 Sampling point diagram of RMG intagliation depth and style should be
16 Form –G : Wet mixing
17 Form –H : Drying examined to ensure that picking of the
18 Sampling point diagram of FBD
19 Form–I : Lubrication intagliation during compression or fill-in
20 Sampling point diagram of RMG
of the intagliation during coating does not
21 Form–J : Compression
22 Form–K : Coating occur.
23 Form–L : Bulk packing
24 Re validation criteria
25 Change control Compression speed: The formulation
26 Stability
27 Deviations should be compressed at a wide range of
28 Conclusion compression speeds to determine the
29 Report and Approval
operating range of the compressor. The
7. Tablet Compression
adequacy of the material’s flow into the
Compression is a critical step in the
dies will be determined by examining the
production of a tablet dosage form. The
tablet weights. Is a force feeder required to

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ensure that sufficient material is fed into tablets will have a rough surface
the dies? appearance. For tablet shape, a round
tablet will be easier to coat than tablets
Compression/ejection force: The
will multiple sides or edges because of the
compression profile for the tablet
uniformity of the surface. For intagliated
formulation will need to be determined to
tablets, the intagliation style and depth
establish the optimal compression force to
should be developed to prevent fill-in or
obtain the desired tablet hardness. The
chipping of the intagliation.
particle size/size distribution or level of
lubricant may need to be adjusted in order Equipment type: The type of coater will
to have a robust process on a high speed need to be selected. Conventional or
compressor. The following in-process tests perforated pan and fluid bed coaters are
should be examined during the potential options.
compression stage: Coater load: Having too large a pan load
1. Appearance could cause attrition of the tablets because
2. Hardness of the overall tablet weight in the coater. In
3. Tablet weight the case of a fluid bed coater, there may
4. Friability
not be sufficient airflow to fluidize the
5. Disintegration tablets.
6. Weight uniformity
Pan speed: This will be interrelated to
8. Tablet Coating other coating parameters, such as inlet
Tablet coating can occur by different temperature, spray rate, and flow rate.
techniques (e.g., sugar, film, or
compression). Film coating has been the Spray guns: The number and types of
most common technique over recent years guns should be determined in order to
and will be the focus of this section. Key efficiently coat the tablets. The spray
areas to consider for tablet coating include nozzles should be sized properly to ensure
the following: even distribution over the tablet bed and to
Tablet properties: Tablet properties such prevent clogging of the nozzles. The
as hardness, shape, and intagliation (if location and angle of the spray gun(s)
required) are important to obtain a good should be positioned to get adequate
film-coated tablet. The tablet needs to be coverage. Having the guns positioned too
hard enough to withstand the coating close together can lead to a portion of the
process. If tablet attrition occurs, the tablets to be over wet.

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Application/spray rate: The optimal

Table 5: Validation team and Responsibilities
application/spray rate should be
Department Designation Responsibility
determined. Spraying too fast will cause
Research and Executive/ To coordinate the
Develop-ment Officer entire validation the tablets to become over wet, resulting in
(R&D) process by
scheduling meetings clumping of tablets and possible
and discussions with
production, quality
dissolution of the tablet surface. Spraying
control and quality too slowly will cause the coating materials
assurance.
Preparation of to dry prior to adhesion to the tablets. This
preliminary validation
protocol, master will result in a rough tablet surface and
formula record,
monitoring the poor coating efficiency.
process, compiling
and analyzing data Tablet flow: The flow or movement of the
and test results and
preparing the final tablets in the coater should be examined to
report.
To review the ensure proper flow and even distribution
preliminary validation
of the coating solution onto the tablets.
documents.
Quality Officer To coordinate the The addition of baffles may be required to
assurance entire validation
process by provide adequate movement of tablets for
scheduling meetings
and discussions with tablet coating.
the team.
Preparation of
validation protocol,
Inlet/outlet temperature and airflow:
monitoring the These parameters are interrelated and
process, compiling
and analyzing data should be set to ensure that the atomized
and test results and
preparing the final coating solution reaches the tablet surface
report.
To review of and then is quickly dried.
validation documents.
Coating solution: The concentration and
Production Officer To participate in
performing the viscosity of the coating solution will need
validation steps
during manufacturing to be determined. The solution will need to
processes.
To assist in
be sufficiently diluted in order to spray the
collection of data. material on the tablets. The concentration
Quality Officer To test and report
control the test results of the coating solution will also determine
Quality General To approve the
assurance manager process validation the amount and volume of solution to be
protocol and report.
Quality To review of applied to the tablets. The stability of the
assurance validation documents. coating solution should be investigated to
To approve the
process. establish its shelf life.

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Sr. No. Steps Control Variable Critical Acceptance criteria

Parameters
to be checked
1 Dry mixing Time Mixing time Mixing time: ………………min.
Impeller speed and speed Impeller speed:
(slow/medium/high)±5RPM.
Content uniformity: 90%-110%
RSD : ±5%
2 Binder Time Mode and time Depending up on the
preparation and of formulation.
Temperature,
addition. addition
Solvent used
3 Kneading Time Mixing time Impeller speed:
and (slow/medium/high)
Impeller speed & speed Chopper speed:
Chopper speed (slow/medium/high)
Depending up on the
formulation.

4 Drying Inlet/outlet Inlet/outlet Initial drying:……………..0C

temperature & time temperature & Drying time: ……………min.
Drying time Final drying : ………….0C±50C
Loss on drying : …………….%
below 3% or depending on
formulation
5 Lubrication Time Mixing time Mixing time: ……………min.
Blender/granulator and speed Speed: slow……………..rpm.
speed Content uniformity :
Physical parameters – for
information.
6 Compression Pressure and turret Machine speed Average weight:
speed and mg±5%,7.5%,10%.
compression Uniformity of weight mg :
pressure Thickness : ………….mm
Hardness : …………..KN or
Kg/cm2
Disintegration time:
NMT…..min.
Friability : NMT…………%w/w
Assay : As per the label claim
Dissolution:…………….%
7 Coating Pan speed and spray Pan speed Average weight : …………..
rate Inlet & outlet mg±5%
temperature Weight of 20 tablets :……..mg
Spray rate Thickness : ………….mm
Disintegration time:
NMT…..min.
Assay : As per the label claim
Dissolution: …………….%
Coating weight: A minimum and great enough to cause fill-in of the
maximum coating weight should be intagliation.
established for the tablet. Sufficient Residual solvent level: If solvents are
coating material should be applied to used for tablet coating, the residual
the tablets to provide a uniform solvent level will need to be
appearance; however, it should not be determined.

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Appearance testing of the tablets is is program within an industry. The

critical during the coating operation. Items multidisciplinary validation team must
to look for include the following: identify the product and process
1. Cracking or peeling of the coating characteristics that must be studied and
2. Intagliation fill-in incorporate specific validation tests to
3. Surface roughness ensure that that product will meet all
4. Color uniformity quality, manufacturing, and regulatory
5. Coating efficiency should be determined requirements. The total program should
for the coating operation. The efficiency begin with validation of the active
will determine the amount of coating pharmaceutical ingredient
solution overage that may be required. (API) characteristics so that this material
will be uniform batch after batch,
9. In-process tests
providing a solid footing upon which the
1. Moisture content of “dried granulation”
dosage form will be built. Scientific
2. Granulation particle size distribution
information obtained during the
3. Blend uniformity
preformulation stage can form the basis for
4. Individual tablet/capsule weight
a well-designed and comprehensive
5. Tablet hardness
validation program. The parameters
6. Tablet thickness
chosen must be relevant indicators of a
7. Disintegration
controlled process. It is not sufficient
8. Impurity profile
merely to devise a test and set
10. Finished product tests specifications for it; rather, it is desirable
1. Appearance to show a cause and effect relationship
2. Assay between the parameter tested and control
3. Content uniformity of the quality and/or process output.
4. Tablet hardness Continued awareness of validation
5. Tablet friability requirements and a diligent application of
6. Impurity profile validation principles will thus help to
7. Dissolution ensure that pharmaceutical products will

CONCLUSION be able to be developed and produced with

Solid dosage form validation should be the quality and reproducibility required

part of a comprehensive validation from regulatory agencies across the world.

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REFERENCE: tablet dosage form”,Int J Xeno Pharm

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