contract laboratory .com - FDA GMP, GCP, ICH GLP labs or Contract Research Organizations CRO's for USP, EP, ISO, GLP ICH, DEA, analytical chemistry, pharmaceutical, toxicity, toxicology, clinical research, product safety, microbiology, pharmacology, pharmacogenomics, bioanalytical, sterility,  stability, pK, pharmacokinetic, ADME, ADMET,  clinical testing, formulation studies, deformulation, reverse engineering, shipping studies, research and development, analysis, experiments, methods validation, methods development, quality control QA/QC of OTC, Rx, pharmaceutical drug API, ingredient, in-process, finished products, raw materials, packaging.
Find US FDA, GMP, GLP, GCP, ISO, CLIA, ASTM, AOAC, AAALAC, A2LA, and UKAS Labs for all your Pharmaceutical Testing and Research !
P Formulate .com pharmaceutical formulation, pharmaceutical research and development, pharmaceutical testing, pharmaceutical manufacturing, pharmaceutical supplier, pharmaceutical active pharmaceutical ingredient, deformulation, reverse engineering, pharmaceutical excipient resources on the web.

Pharmaceutical Formulation Databases and Resources

Pharmaceutical Excipient Databases

P formulate What?
Pharmaceutical Formulation Services
Pharmaceutical Excipient Suppliers
Pharmaceutical Excipient and Formulation Resources

--Pharmaceutical Binders

--Pharmaceutical Coatings

--Pharmaceutical Colors and Colorants

--Pharmaceutical Compression Aids

--Pharmaceutical Disintegrants

--Pharmaceutical Emulsifying Agents

--Pharmaceutical Encapsulation Aids

--Pharmaceutical Fillers

--Pharmaceutical Gums

--Pharmaceutical Liquid Vehicles

--Pharmaceutical Lubricants

--Pharmaceutical Plasticizers

--Pharmaceutical Preservatives

--Pharmaceutical Spheronization Agents

--Pharmaceutical Suspending Agents

--Pharmaceutical Sweeteners

--Pharmaceutical Wet Granulation Agents

Contact p Formulate .com
p Formulate .com Pharmaceutical Advertising and Marketing

 

 


 

 

 

 

 

 

 


 

 


 

 

p Formulate What?

p Formulate a Softgel


Basic formulation information on formulating, developing and manufacturing softgel pharmaceutical or nutritional products. If you have a specific question, please email us
 
 
1] What is a softgel?  

A softgel (a.k.a., a soft gelatin capsule) is a solid capsule (outer shell) surrounding a liquid or semi-solid center (inner fill). An active ingredient can be incorporated into the outer shell, the inner fill, or both. 

 
2) Advantages of softgels:
Ease of Use Easy to swallow, no taste, unit dose delivery, tamper-proof
Versatile Wide variety of colors, shapes, and sizes. 

Accommodates a wide variety of compounds filled as a semi-solid, liquid, gel or paste.

Immediate or delayed drug delivery.

Can be used to improve bioavailability by delivering drug in solution or other absorption enhancing media.

 

3) Disadvantages of softgels:

Requires special manufacturing equipment

Stability concerns with highly water soluble compounds, and compounds susceptible to hydrolysis

Limited choices of excipients/carriers compatible with the gelatin

4) The outer shell is composed of a gelatin or potato starch matrix.

 

Gelatin matrix consists of gelatin, plasticizer, solvent and optional ingredients such as flavors and colorants.

 

Gelatin - bovine, porcine, or piscine (fish) origin. Comes in a variety of bloom strengths, the higher the bloom strength, the more resilient the gel. Most oil based fills are encapsulated using a bloom strength of 150. When polyethylene (PEG) based fills are used, a higher bloom strength is generally used.

The limitations of bovine (i.e. bovine-related diseases) and porcine (i.e. not kosher) gelatin may be overcome by piscine (fish) gelatin.   

Plasticizer - Glycerin and Sorbitol Special are the two most common plasticizers. Glycerin is generally used with oil based fills. Sorbitol Special is used with PEG based fills. Sorbitol is not soluble in PEG and therefore will not leach out of the shell into the PEG based fill like Glycerin would. Sorbitol Special is formulated to inhibit sorbitol from crystallizing out in the gelatin shell. Do not substitute Sorbitol for Sorbitol Special.

Solvent - Water

Optional Ingredients - 

Colors

Flavors

Potato starch matrix
This is a smooth, transparent substance resembling gelatin, which is neutral in taste and color, easily digestible and of plant origin, and therefore, the concerns of certain bovine related diseases are not an issue, and they offer a gelatin free alternative for vegetarians and vegans. Currently, available from Swiss Caps under the name Vegagels®.   

 

5] There are three primary types of inner fill materials:     

 

Neat Substance, especially oily liquids

 

Solution Fills: Active dissolved in a carrier

 

Oils such as soybean oil and Miglyol 812 (neutral oil, triglycerides of medium chain fatty acids)

Polyethylene Glycols: especially PEG 400 -600

Other solvents: Any other solvent which doesn't degrade or solubilize the gelatin shell, i.e., dimethyl isosorbide, surfactants, diethylene glycol monoethly ether 

Optional Ingredients:

Water or alcohol: up to 10% w/w, if needed for solubility

Glycerin: 1 to 4% w/w to retard the migration of the glycerin out of the shell into the fill

Polyvinylpyrrolidone: Up to 10% w/w used in combination with PEG, can increase drug solubility, and also improve stability by inhibiting drug recrystallization 

Suspension Fills: Active dispersed in a carrier

 

Suspensions can accommondate about 30% solids before viscosity and filling become a problem

Suspensions can be heated up to 35ºC to decrease viscosity during the filling process

Suspended solids must be smaller than 80 mesh -- mill or homogenize before filling to prevent needles from clogging during filling.

Carriers

Oily mixtures:

  1. Traditional: Soybean Oil with beeswax (4-10% w/w) and lecithin (2-4% w/w). The lecithin improves material flow, and imparts some lubrication during filling. Add enough beeswax to get a good suspension, but avoid creating a non-dispersible plug. 

  2. Gelified Oil (e.g. Geloil® SC), a ready to use system composed of soybean oil, a suspending agent, and a wetting agent. Simplifies the manufacturing process, and avoids batch to batch and supplier to supplier variability.  

Polyethylene glycol

PEG 800 -1000 for semi-solid fills

PEG 10,000 -100,000for solid fills

Or mixtures of the above.

Heat up to 35ºC to make fluid enough for filling.

Glycerides

  1. Glycerides of long chain fatty acids (e.g. Gelucire® 33/01). Hydrophobic with surfactant properties.

Optional Ingredients:

  1. Surfactant: sorbitan derivatives such as polysorbate 80 or lecithin.

  2. For hydrophobic drugs dissolved or dispersed in an oily matrix, a surfactant of HLB 10 will increase the dispersibility of the product in aqueous fluids and also may improve bioavailability.

 

6] Incompatibilities:
Avoid aldehydes which can lead to cross linking (pellicle formation) of the gelatin, and poor dissolution of the gelatin capsule in water. This may be overcome by adding enzymes to the dissolution media, (see FDA Guidelines)
Drugs sensitive to water can degrade (e.g. ranitidine) or undergo polymorphic conversion (e.g. terazosin). 
Compounds (especially those of high water solubility) can migrate from the fill into the shell or get trapped in a hydrophobic matrix resulting in poor dissolution and loss of bioavailability. 

 

Need a supplier of excipients, ingredients, packaging materials or eqquipment to formulate, develop or manufacture a soft gel pharmaceutical or nutritional product? Submit in Excipients Express!!!


7) Soft Gelatin Encapsulation Processes and Equipment 

Rotary Die process

Two ribbons of gelatin are fed continuously into a rotating die assembly and are simultaneously formed into the two halves of a capsule. The ribbons converge adjacent to a fill injector. The fill injector is actuated by a pump which measures and dispenses the appropriate volume of fill material into the capsules. The filled capsules are subsequently sealed as the die assembly rotates. This process permits accurate and reproducible fill uniformity.

Pump heads are available for fill weights as low as 100 mg. For oral dosage forms, the fill weight ranges from 100 mg up to about 1 gram.    

The following should be monitored/controlled:

Gelatin temperature
Fill temperature
Ribbon thickness
Seal or seam width
Fill quantity

Following encapsulation, the capsules undergo drying in a tumble drying tunnel with an elevated temperature and a large volume of forced air. From the drying tunnel, the capsules are transferred onto trays and placed into a low humidity drying room.

The following should be monitored:

Gelatin moisture
Fill moisture
Capsule hardness  

Drying is a dynamic process, and the goal is to have the gelatin shell return to it's equilibrium moisture content in the range of 6 - 8%.

Oil fills dry faster than PEG fills, and typically reach a shell moisture content of 6 to 8% within 24 hours.   

If water migrates into the fill, it needs to migrate back out or at lease be in equilibrium  with the moisture content of the shell for good stability. This is more typical of the PEG fills. These can take 7 to 10 days to reach acceptable moisture levels, and may still contain up to 10% water after drying. 

Are you a manufacturer or supplier of pharmaceutical grade, USP grade or food grade ingredients, chemicals, or packaging materials used in soft gel pharmaceutical or nutritionals ? If so , email us at pformulate@pformulate.com to find out how to have your products listed in our soft-gel directories.

 

Pformulate/01/02/2003

   
--
p Formulate Film Coatings
--
p Fformulate Softgels
--
p Fformulate Tablets
--
p Fformulate Gluten-free
--
p Formulate Gums
Excipient's Express
Need to find a supplier to formulate a film coating, softgel, tablet, gluten-free or gum based pharmaceutical or nutraceutical ? Simply submit in Excipients Express Requests !

P formulate

527 NE 57th Street Miami, FL  33137

Phone: 305-756-6267

pformulate@pformulate.com

Owned and operated by Janice L. Cacace, Ph.D., 

a consultant to the pharmaceutical industry with over 20 years of pharmaceutical and nutraceutical research, development, formulation and manufacturing experience.