Method of Sterilization

Methods of Sterilization:

Definition: Sterility is the absence of viable microorganisms. It is essential that the effect of the chosen sterilization procedure on the product (including its final container or package) is investigated to ensure effectiveness and therefore the integrity of the product, which the procedure is valid before being applied in follow. guaranteeing that the selection of the instrumentality is like to permit the optimum sterilization to be applied.

Steam Sterilization:

Applicable Products: Large Volume Parenteral Liquids.

Definition: Sterilization is finished by saturated steam struggling particularly for binary compound preparation. The reference conditions for binary compound preparations ar heating at a minimum of 1210C for quarter-hour. different mixtures of your time & temperature could also be used providing it's been satisfactorily incontestible that the method chosen delivers AN adequate and duplicable level of unwholesomeness once operational habitually among the established tolerances. The procedures and precautions utilized ar like to administer a SAL (Sterility Assurance Level) of 10-6 or higher. Spores of B stearothermophilus ar suggested for validation. there's no growth of the reference microorganisms once the biological indicators are exposed to steam at 121±10C for fifteen min.

Time at Temp. Cycles for Moist Heat Sterilization are given in Table-1

Table-1

Temperature (0C)	Pressure (p.s.i.)			Minimum Holding Time (min)
	(kPa)abs	(lbf/in2)g	(bar)
115-116	172	10	1.7	30
121-123	202	15	2.0	15
126-129	242	20	2.4	10
134-138	304	32	3.0	3
106			1.6	85

      

        Ref: BP 2004, Vol.-4,  and Pharmaceutical Practice

Ethylene Oxide Gas Sterilization:

 

Applicable Products: Infusion Sets, Syringes and Scalp Vein Sets.

Definition: Ethylene Oxide is extremely effective at killing microorganisms and its activity is related to its action as an alkylating agent. Reactive hydrogen atoms on hydroxyl, carboxyl, sulphydril & amino groups can all be replaced with hydroxyethyl groups thus interfering with a wide range of metabolic activities. It is essential that penetration by gas and moisture into the material to be sterilized is ensured and followed to elimination of the gas. where attainable, the gas concentration, ratio, temperature and period of the method area unit measured and recorded.. Measurements are made where sterilization conditions are least likely achieved, as determined at validation. Spores of Bacillus subtilis var. niger are recommended for validation.

Concentration of Ethylene Oxide & Time of Exposure: Manufacturer of ethylene oxide sterilizer recommends, for most purposes, exposure to 850-900 mg/l for 3 h or 450 mg/l for 5 h, at 54⁰C. A powerful vacuum immediately is to be applied after sterilization, e.g. 1.5 kPa (15 mbar) for 2 hours. Also partial vacuums are applied to about 20 kPa (0.2 bar) and then admit sterile air to atmospheric pressure as a flushing agent. This is repeated for 5 to 6 times.

Different Factors responsible for EO Gas sterilization are given in Table-2.

Table-2

EO Gas Sterilizer	Temp.	Pressure (mbar)/ Gas Conc.	Relative Humidity	Time (HoldingTime)
Standard	540C	450 mg/L	50%	5 hours
Standard	540C	850-900mg/L	50%	3 hours
For Biological Indicator	540C	600 mg/L	60%	60 min.
At Infusion Set	450C	800/150 mbar	60%	240 min
At Syringe	310C	900/525 mbar	60%	60 min

   Ref: BP 2004, Vol.-4,  & Pharmaceutical Practice,

Dry Heat Sterilization:

Applicable Particulars: Glass Apparatus.

Definition: Sterilization by dry heat is usually carried out in a hot air oven in which heat is transferred from its source to the load by radiation, convection and to a small extent by conduction. Spores of Bacillus subtilis var. niger are recommended for validation

 Time Temperature Combinations:

·        minimum one hundred eighty degree Celsius  for not less than 30 minutes

·       minimum one hundred seventy degree Celsius for not less than 1 hour

·        minimum one hundred sixty degree Celsius for not less than 2 hours

For Depyrogenation of the Glassware, Treatment is done at 250⁰C for 30 minutes or 200⁰C for 1 hour.

Ref.: Pharmaceutical Practice and BP 2004, Vol.-4.

Binding Agent

Binding Agent

Binder:

 Binders are adhesive materials used to hold powders together as granules & to assist in ultimately holding the compressed tablet together.

Binder is of two types:

-         Solution binder

-         Dry binder.

Solution Binders :

 

-         Starch paste (10-17%)

-         Gelatin solution (10-20%)

-         Sucrose syrup (50-85%)

-         Glucose solution (50% alcohol, 25% glucose and 25% water)

-         Methyl cellulose 4% in alcohol.

-         Ethyl cellulose 5% in alcohol.

-         Starch- acacia paste( starch 5%, acacia 2% in water)

-         Sodium CMC.

-         PVP in aqueous, alcoholic and hydro alcoholic solⁿ

-         Polyethylene glycol.

Dry Binder:

 

-         Cellulose

-         Methyl cellulose

-         PVP

-         Polyethylene Glycol.

Antioxidant

Anti-oxidant: 

It helps to prevent oxidation. Its transfers electron or hydrogen from a substance to an oxidizing agent. 

For example:

Anti-oxidant (reducing agents):  Sodium bi sulphate / Butylated anisole / Thiourea 

Anti-oxidant (blocking agents):  Tocopherol / Ascorbic acid esters.

Synergist : Ascorbic acid (vitamin – C) / Phosphoric acid / Tartaric acid / Citric acid

Lamination in Tablet

Lamination:

Lamination is that the separation of a pill into 2 or additional distinct horizontal layers.

Reason: These issues occur owing to meagerly binder, improper granulation, layering of granules. Pressure personality disorder, defense of air into the entire of the pill, war punch, lack of enough fine powders.


The Causes and Remedies of Lamination associated with ‘Formulation’ (granulation).
  
CAUSES:
   
1.   Oily or waxy materials in granules.   
2.  Too much of hydrophobic material e.g.: Magnesium-stearate.
   
REMEDIES:

1. Modify combining method. Add adsorbent or absorbent.
2.  Use a less quantity of material or amendment the sort of material.

 
The causes and remedies of lamination associated with ‘Machine’ (dies, punches and pill press).

CAUSES:
   
1.   Rapid relaxation of the peripheral regions of the pill, on ejection of the die.
2.   Rapid decompression
   
REMEDIES:

1. Use tapered dies, i.e. higher a part of the die bore has Associate in Nursing outward taper of 3° to 5°.
2.  Use pre-compression step. scale back turret speed and scale back the ultimate compression pressure.

Picking in tablet

 Picking:  

Definition: ‘Picking’ is that the term used once atiny low quantity of fabric from a pill is protrusive to and being removed aloof from the tablet-surface by a punch face.

The problem is additional current on the higher punch faces than on the lower ones. the matter worsens, if tablets ar repeatedly factory-made during this station of tooling owing to the additional and additional material obtaining more to the already stuck material on the punch face.

Reason: choosing is of explicit concern once punch tips have engraving or embossing letters, moreover because the granular material is badly dried.


The causes and remedies of choosing associated with ‘Formulation’ (granulation).


CAUSES
   
1    Excessive wet in granules.   
2   Too little or improper lubrication.  
3  Low freezing point substances, could soften from the warmth of compression and cause choosing.   
4  Low freezing point drug in high concentration.
5  Too heat granules once pressing.  
6  Too much quantity of binder.
   

REMEDIES:

1.  Dry properly the granules, confirm optimum limit.
2.  Increase lubrication; use mixture silicon dioxide as a ‘polishing agent’, so material doesn't hold tight punch faces.
3.  Add high melting-point materials. Use high meting purpose lubricants.
4.  Refrigerate granules and also the entire pill press.
5.  Compress at temperature. Cool sufficiently before compression.
6.  Reduce the number of binder, amendment the kind or use dry binders.


The causes and remedies of choosing associated with ‘Machine’ (dies, punches and pill press).
   
CAUSES:   
1.  Rough or scraped punch faces. 
2.  Embossing or engraving letters on punch faces like B, A, O, R, P, Q, G.   
3.  Bevels or dividing lines too deep.
4.  Pressure applied isn't enough; too soft tablets.
   

REMEDIES:

1.  Polish faces to high luster.
2. Design inscription as massive as attainable. Plate the punch faces with metal to provide a sleek and non-adherent face.
3.  Reduce depths and sharpness.
4.  Increase pressure to optimum.

Self Inspection

What is self inspection?

Self inspections ought to be conducted so as to observe the implementation and compliance with sensible producing observe principles and to propose necessary corrective measures.

Formulation of the Aceclofenac Tablet

Formulation of the Aceclofenac Tablet:

Aceclofenac tablet :  This tablet have round shape and film coated.

Name of  the Raw Materials	Specifications	Quantity
Aceclofenac	BP	100 mg
Maize Starch	BP	75 mg
Povidone-k-30	BP	8.35 mg
Sodium Starch Glycolate	BP	5 mg
Purified Talc	BP	1.65 mg
Lactose	BP	107 mg
Magnesium Stearate	BP	3 mg