Assignment - 1

Submitted to: Dr. Navaz

Submitted by: Shaik Md Haneef

Regd.no: 19L81S0403

raghavendra institute of pharmaceutical education and research , Anantapur.

 INTRODUCTION TO CAPSULE:
The word ‘Capsule’ derived from the Latin word “capsula”, which means a small box or
container. The word occurs in many scientific disciplines, ranging from anatomy, as an
enclosing membrane andin botany, as a descriptive word for fruit, to astrophysics, as a
space vehicle. In pharmacy, capsule word has been used to describe a glass ampule and
also as a name of protective cap over the stopper of a bottle of medicine. In more recent
times, capsule has been used primarily to describe solid dosage forms, which consist of
a container, filled with medicinal substance. They can be divided in maintwo categories,
hard capsule (two pieces) and soft capsule (one piece) according to the presence of
glycerol or another plasticizer which make it soft and elastic. The soft gel dosage form
has been around for many years. The earliest soft gels date back to the 19 thcentury. Since
then, many improvements have been made with respect to the production of these soft
capsules. Soft gel manufacturing still requires special skills and equipment that less than
a handful of companies can offer to pharmaceutical clients. Notwithstanding the
progress that has been made in soft gel manufacturing, the soft gel as a dosage form has
remained largely unchanged over the years. As a result, patent protection on the
technology was lost, which is a disadvantage in the era of pharmaceutical life-cycle
management. For that reason, Banner has developed new soft gel variants that not only
offer specific benefits over the standard soft gel, but also provide additional patent
protection to the compounds theydeliver.
Since the introduction of Soft Capsule Making Machine in the 1970s, formulations
have continually become more popular with rapid developments in recent years. This
could be illustrated by emergency of a more than 560 sets of Soft Capsule Making
Machine with transfer mode having a production rate of up to 60 billion pills/year (i.e.
more than 3600 kinds of drugs) in the world.3 Up to now, there are more than 30
manufacturers producing more than 40 kinds of soft capsules by using over 60 sets of
advanced machines.4 Soft gels ability to enhance bioavailability not only makes them
the preferred dosage form for new chemical entities with poor oral bioavailability, they
can also be used for reformulation of existing drugs, with the purpose of life-cycle
extension.

Drug Candidates for Capsule: -

 Drugs which are having Poor bioavailability i.e.Digoxin
 Drugs which are having Low melting point i.e. Ibuprofen and Vitamins
 Drugs which are having Low dose / Highpotency.
 Drugs which are having Contentuniformity.
 Drugs which are having Critical stability i.e. the antibiotic
Vancomycinhydrochloride
 Drugs which are having Sustained release. i.e.Gelucire
 DrugswhicharehavingShorthalf-life.i.e.penicillinG
 Drugs which are having Short long life. i.e.Diazepam.
 Drugs which requires large doses i.e.Sulphonamides.
 Drugs which are having extensive plasma proteinbinding.

Drug used for Capsule: -

 Digoxin
  Ibuprofen
 Vancomycin
 Gelucire
 PenicillinG
 Diazepam
 Sulphonamides
 Phenytoin
 Furosemide
 Paracetamol
 Diclofenac

Capsule:

Capsules are a solid dosage form in which the drugs substance is enclosed in a
water-soluble shell or an envelope. A Capsule shell is made from Gelatin.

Types of Capsules:

1) Hard Gelatin Capsule

2) Soft Gelatin Capsule

Advantages of Capsules

1. Ease of use due to the fact that it is smooth, slippery and easy to swallow.

2. Suitable for substances having bitter taste and unpleasant odor.

3. As produced in large quantities it is economic, attractive and available in wide range of

colors.

4. Minimum excipients required.

5. Little pressure required to compact the material.

6. Unit dosage form.

7. Easy to store and transport.

Disadvantages of Capsules

1. Not suitable for highly soluble substances like potassium chloride, potassium bromide,
ammonium chloride, etc.

2. Not suitable for highly efflorescent or deliquescent materials.

3. Special conditions are required for storage.

4.hygroscopic drug cannot be filled in capsules.

Hard Gelatin Capsules

Hard gelatin capsules, unlike the soft form, are made of two parts, the body and the cap,
each of a different colour. This form of capsule holds dry ingredients in powder form.
The body is first filled with the mix of active ingredients and any excipients used, and
then closed with the cap using either a manual or automatic press machine.

Once ingested, the hard capsules disintegrate within three minutes and quickly release the
drug inside. Hard gelatin capsules are also hygroscopic and contain a higher water
content than the soft capsules at around 12-15%.

Some drugs need to be released at certain points in the body, and therefore the capsule
must release the drug at an earlier time. To enable this, the capsule can be filled with
target release pellets. As well as powdered ingredients, the gelatin capsules can also be
used to cover premade tablets.
Soft Gelatin Capsules

Also called softgels, soft gelatin capsules are a case produced from a single piece of
gelatin, rather than two halves attached together. They are used for solutions not based on
water, as this would dissolve the gelatin, but for oil based solutions. The active
ingredients is dissolved in the oil-based solution, and once the capsule is ingested, it
dissolves within the body, releasing the drug. The capsule dissolves within minutes of
reaching the stomach. The soft gelatin capsule is manufactured and filled using the same
machine as part of a single process, and some have the brands or dosage strength printed
on then. Gelatin is hygroscopic in nature, and the gels contain between 5-14% water.

Excipients used in filling of Capsules

1 Diluents

2 Absorbents
3 Glidants

4 Anti dusting Compounds

Method of filling the hard gelatin capsules:-

The capsules can be filled either by hand or by a semi-automatic device or by an

automatic filling machine.

Capsule filling machine (Hand operated )-It consists of:-

1 A bed having 200-300 holes.

2 A loading tray having 200-300holes

3 A powder tray

4 A pin plate having 200-300 pins

5 A sealing plate having a rubber top

6 A lever

7 A cam handle

The empty capsules are filled in the loading tray and it is placed over the bed.The cam
handle is operated to separate the capsule caps from their bodies.The powder tray is
placed in a proper position and filled with an accurate quantity of powder with
scraper.The excess of powder is collected on the platform of the powder tray.The pin
plate is lowered and filled powder is pressed by moving the pin downwards.After
pressing ,the pin plate is raised and the remaining powder is filled into the bodies of
capsules.The powdered tray is removed after its complete filling.The cap holding tray is
again placed in position .The plate with the rubber top is lowered and the lever is
operated to lock the caps and bodies.The loading tray is then removed and the filled
capsules are collected.
With a 200 hole machine ,about 5000 capsules can be filled in one hour,whereas in a
machine having 300 holes ,about 7500 capsules can be filled in one hour.

Method of filling the Soft gelatin capsules:-

Step #1: Preparing Gelatin

Step #2: Prepare Fill Material

Step#3: Begin the Encapsulation Process

Step #4: Further Processing of Filled Soft Gelatin Capsules

Differences between Hard Gelatin and Soft Gelatin Capsules

Storage of Capsules:

A capsule is a very sensitive product and it must be protected against excessive heat and
humidity. For storage we recommend a temperature between 15 to 25 C and a relative
humidity between 35 and 65%. ... To maintain the capsules initial specifications,
temperature and relative humidity have to be adjusted together

Containers :

Capsules should be dispensed in tightly closed glass or plastic container protected from
dust and from extremes of humidity and temperature.

Evaluation of Capsules

1. Percentage Yield
The percentage yield of the granules was determined for drug and was calculated
using the followimg equation Where, M = weight of granules and Mo = total
expected weight of polymer.
2. Angle of Repose:
Angle of repose (α) was determined using funnel method. The blend was poured
through a funnel that can be raised vertically until a maximum cone height (h) was
obtained. The radius of the heap (r) was measured and angle of repose was
calculated:

α = tan Ǧ1 (h/r)

3. Bulk Density:
 Apparent bulk density (ρb) was determined by placing presieved drug excipients
blend into a graduated cylinder and measuring the volume (Vb) and weight (M) “as
it is” ρb = M/Vb
4. Tapped Density;
The measuring cylinder containing a known mass of blend was tapped for a fixed
number of taps. The minimum volume (Vt) occupied in the cylinder and the weight
(M) of the blend was measured. The tapped density (ρt) was calculated using
following formula: ρt = M/ Vt
5. Hausner’s Ratio
Hausner’s ratio is an index of ease of powder flow; it is calculated by following
formula:

Hausner’s ratio = ρt\ ρb

Where, ρt = Tapped density and ρb = Untapped bulk density

6. Carr’s Index
The simplest way of measurement of free flow property of powder is
compressibility, an indication of the ease with which a material can be induced to
flow is given by % compressibility which is calculated as follows:

C = (ρt – ρb) / ρt * 100

Where, ρt = Tapped density and ρb = Untapped bulk density

7.Weight variation test

Ten capsules were individually weighed and the contents were removed. The emptied
capsules were individually weighed and the net weight of the contents was calculated by
subtraction and the percent weight variation was calculated by using the following
formula15:
Weight variation = (Weight of capsule-Average weight) ×100

Average weight of capsules

Weight variation should not be more than 7.5 %

8. Disintegration

The capsules were placed in the basket rack assembly, which isrepeatedly immersed 30
times per minute into a thermostatically controlled fluid at 37°C. To fully satisfy the test,
the capsules should disintegrate completely into a soft mass having no palpably firm core
without any fragments of the gelatin shell. If one or two capsules fail, the test should be
repeated on additional of 12 capsules. Then, not fewer than 16 of the total 18 capsules
tested should disintegrate completely

9.Dissolution studies

Dissolution is a process by which the disintegrated solid solute converted into solution.
The test determines the time required for a definite percentage of the drug in capsules to
dissolve under specified conditions. The release of drug was determined using a
dissolution apparatus of USP Type II (paddle) at 50 rpm. 900 ml of 0.1N hydrochloric
solution acid was used as the dissolution medium and were maintained at the temperature
of 37.5 } 0.5°C. A sinker was used to avoid capsule flotation 14. The samples were
drawn at 5, 10, 15 30 and 45 mints and equal amount of fresh medium were replaced to
maintain the sink conditions. Samples withdrawn were analyzed to determine the
percentage of drug released.

10.Stability Studies
Stability of the drug has been defined as the ability of particular formulations, in a
specific container, to remain within its physical, chemical, therapeutic and toxicological
specification. The purpose of stability testing is to provide evidence on how the quality of
a drug substance or drug product varies with time under the influence of a variety of
environmental factors, such as temperature, humidity etc. The storage conditions for
stability studies were accelerated Condition (40 } 2°C / 75 } 5 % RH) and Long term
condition (25 } 2°C / 60 } 5 % RH). The capsules were packed as 30’s count in
HDPE containers, induction sealed with adsorbent cotton 26-29.

11.Uniformity of content

Five capsules were weighed and their contents were removed. An accurately weighed
sample equivalent to 100 mg of drug was taken in a volumetric flask (100 ml). The
content was dissolved in 0.1N HCl and the volume made up to 100 ml. This solution was
filtered through Watt man filter paper No.41. The solution was diluted and the
absorbance was measured at 274.0 nm. The drug content was calculated.

Application

• This technology is applicable for GI diseases like GI cancers, Crohn’s disease and
acid reflux. It can even be used in case of diabetes.

• Targeted release by the use of magnet helps the drug’s uptake and bioavailability
without damaging intestinal tissues.

• Magnetic localization of chemotherapeutics at the site of GI tumors, which are

simultaneously identifiable on X-ray following intravenous administration of radio
opaque contrast, would enable localized dosing while minimizing side effects associated
with systemic administration.
• It provides a fast, cost-effective, and convenient means for the controlled release of
drugs to specific sites in the GI tract.

• It can be used to quickly design and complete a study in either a preclinical (animal
model) or clinical setting.

• It allows the release profile to be explored, altered and adapted quickly to

determine up-front optimal release profile (i.e., before committing resources for solid
dosage form development).

• As an oral dosage form of ethical or proprietary products for human or veterinary

use.

• As a suppository dosage form for rectal use, or for vaginal use.

• As a specialty package in the tube form, for human and veterinary single dose

• Application of topical, ophthalmic and optic preparations, and rectal ointments.