• Capsule Manufacturing Equipment
• Pharma Capsules

In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are:

• Hard-shelled capsules, which contain dry, powdered ingredients or miniature pellets made by e.g. processes of extrusion or spheronization. These are made in two halves: a smaller-diameter “body” that is filled and then sealed using a larger-diameter “cap”.
• Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.

Both of these classes of capsules are made from aqueous solutions of gelling agents, such as animalprotein (mainly gelatin) or plant polysaccharides or their derivatives (such as carrageenans and modified forms of starch and cellulose). Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, preservatives, disintegrants, lubricants and surface treatment.

• Lefancaps is the leading manufacturer of gelatin, enteric, and HPMC capsules used by pharmaceutical, nutritional, and drug companies around the world.
• Capsugel is the global leader in capsules and encapsulation technology. For more than 100 years, biopharmaceutical companies have relied on the quality, consistency and functional innovations Capsugel has delivered; today Capsugel produces more than 200 billion capsules for approximately 4,000 customers in over 100 countries.
• Pharma Capsule Manufacturer Top Capsule Manufacturing Companies in India. Pharma Capsule Manufacturers in India – Connecting with the pharma company can be a great business opportunity for yourself. Have you decided to connect yourself with the pharma companies?
• Vegetable capsules are composed of hypromellose, a polymer formulated from cellulose. Or Pullulan, polysaccharide polymer produced from tapioca starch. Manufacturing equipment. The process of encapsulation of hard gelatin capsules can be done on manual, semi-automatic and automatic capsule.
• The choice of a particular soft gelatin capsules manufacturing process will depend on the availability of the machine and production needs. So far, the plate and rotary die process are the most common processes of manufacturing Softgel capsules. The soft gelatin manufacturing process described above is basically the rotary die process.

Manufacturing and filling of soft gelatin capsules are done same time on the same machine. The content of capsule is filled during the manufacturing the shell. These capsules melt within the minutes in the stomach releasing the content having within it. These contain 5% to 14% of moisture content. Capsule Manufacturing Process. In pharmaceutical industry, there are various pharma company manufactures types of machineries for the different process and application as per there specialty. There are vast categories of pharma machineries as each process requires different machineries.

Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication. For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the “caplet”, a portmanteau of “capsule-shaped tablet”^[1], in order to tie this positive association to more efficiently-produced tablet pills, as well as being an easier-to-swallow shape than the usual disk-shaped tablet.

Single-piece gel encapsulation ('soft capsules')[edit]

In 1833, Mothes and Dublanc were granted a patent for a method to produce a single-piece gelatin capsule that was sealed with a drop of gelatin solution. They used individual iron molds for their process, filling the capsules individually with a medicine dropper. Later on, methods were developed that used sets of plates with pockets to form the capsules. Although some companies still use this method, the equipment is no longer produced commercially. All modern soft-gel encapsulation uses variations of a process developed by R. P. Scherer in 1933. His innovation used a rotary die to produce the capsules. They were then filled by blow molding. This method was high-yield, consistent, and reduced waste.

Softgels can be an effective delivery system for oral drugs, especially poorly soluble drugs. This is because the fill can contain liquid ingredients that help increase solubility or permeability of the drug across the membranes in the body. Liquid ingredients are difficult to include in any other solid dosage form such as a tablet. Softgels are also highly suited to potent drugs (for example, where the dose is <100 µg), where the highly reproducible filling process helps ensure each softgel has the same drug content, and because the operators are not exposed to any drug dust during the manufacturing process.

In 1949, the Lederle Laboratories division of the American Cyanamid Company developed the 'Accogel' process, allowing powders to be accurately filled into soft gelatin capsules.

Two-piece gel encapsulation ('hard capsules')[edit]

James Murdock of London patented the two-piece telescoping gelatin capsule in 1847.^[2] The capsules are made in two parts by dipping metal pins in the gelling agent solution. The capsules are supplied as closed units to the pharmaceutical manufacturer. Before use, the two halves are separated, the capsule is filled with powder or more normally pellets made by the process of Extrusion & Spheronization (either by placing a compressed slug of powder into one half of the capsule, or by filling one half of the capsule with loose powder) and the other half of the capsule is pressed on. With the compressed slug method, weight varies less between capsules. However, the machinery required to manufacture them is more complex.^[3]

The powder or spheroids inside the capsule contains the active ingredient(s) and any excipients, such as binders, disintegrants, fillers, glidant, and preservatives.

Manufacturing materials[edit]

Gelatin capsules, informally called gel caps or gelcaps, are composed of gelatin manufactured from the collagen of animal skin or bone.

Vegetable capsules are composed of hypromellose, a polymer formulated from cellulose.or Pullulan, polysaccharide polymer produced from tapioca starch.

Manufacturing equipment[edit]

The process of encapsulation of hard gelatin capsules can be done on manual, semi-automatic and automatic capsule filling machines. Softgels are filled at the same time as they are produced and sealed on the rotary die of a fully automatic machine. Capsule fill weight is a critical attribute in encapsulation and various real time fill weight monitoring techniques such as near-infrared spectroscopy (NIR) and vibrational spectroscopy are used, as well as in-line weight checks, to ensure product quality.^[4]

Standard sizes of two-piece capsules[edit]

See also[edit]

References[edit]

1. ^Safire, William (1986-03-09). 'On Language; The Caplet Solution'. The New York Times. Retrieved 2017-12-06.
2. ^'History of dosage forms and basic preparations'. Encyclopedia of Pharmaceutical Technology. 7. Informa Health Care. 1998. pp. 304–306. ISBN0-8247-2806-8.
3. ^Bill Bennett; Graham Cole (2003). Pharmaceutical Production, an Engineering Guide. IChemE. pp. 126–129. ISBN0-85295-440-9.
4. ^'Pharmaceutical Encapsulation'. PharmaCMC. Archived from the original on 6 October 2016. Retrieved 27 September 2016.

• L. Lachman; H.A. Lieberman; J.L. Kanig (1986). The Theory and Practice of Industrial Pharmacy (Third ed.). Lea & Febiger, Philadelphia. ISBN0-8121-0977-5.

Drug manufacturing is the process of industrial-scale synthesis of pharmaceutical drugs by pharmaceutical companies. The process of drug manufacturing can be broken down into a series of unit operations, such as milling, granulation, coating, tablet pressing, and others.

• 1Scale-up Considerations
• 2Unit operations

Scale-up Considerations[edit]

Cooling[edit]

While a laboratory may use dry ice as a cooling agent for reaction selectivity, this process gets complicated on an industrial scale. The cost to cool a typical reactor to this temperature is large, and the viscosity of the reagents typically also increases as the temperature lowers, leading to difficult mixing. This results in added costs to stir harder and replace parts more often, or it results in a non-homogeneous reaction. Finally, lower temperatures can result in crusting of reagents, intermediates, and byproducts to the reaction vessel over time, which will impact the purity of the product.^[1]

Stoichiometry[edit]

Different stoichiometric ratios of reagents can result in different ratios of products formed. On the industrial scale, adding a large amount of reagent A to reagent B may take time. During this, the reagent A that is added is exposed to a much higher stoichiometric amount of reagent B until it is all added, and this imbalance can lead to reagent A prematurely reacting, and subsequent products to also react with the huge excess of reagent B.^[1]

Solvent Extractions[edit]

Whether to add organic solvent into aqueous solvent, or vice versa, becomes important on the industrial scale. Depending on your solvents, emulsions can form, and the time for your layers to separate can be extended if the mixing between solvents is not optimal. When adding organic solvent to aqueous, stoichiometry must be considered again as the excess of water could hydrolyze organic compounds in only mildly acid base conditions. In an even wider scope, the location of your chemical plant can play a role in the ambient temperature of your reaction vessel. A difference of even a couple of degrees can yield much different levels of extractions between plants located across countries.^[1]

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Unit operations[edit]

Formulation and pre-formulation development[edit]

Powder feeding in continuous manufacturing[edit]

In continuous manufacturing, input raw materials and energy are fed into the system at a constant rate, and at the same time, a constant extraction of output products is achieved. The process performance is heavily dependent on stability of the material flowrate. For powder-based continuous processes, it is critical to feed powders consistently and accurately into subsequent unit operations of the process line, as feeding is typically the first unit operation.^[2] Feeders have been designed to achieve performance reliability, feed rate accuracy, and minimal disturbances. Accurate and consistent delivery of materials by well-designed feeders ensures overall process stability. Loss-in-weight (LIW) feeders are selected for pharmaceutical manufacturing. Loss-in-weight (LIW) feeders control material dispensing by weight at a precise rate, and are often selected to minimize the flowrate variability that is caused by change of fill level and material bulk density. Importantly, feeding performance is strongly dependent on powder flow properties.^[3][4]

Powder blending[edit]

In the pharmaceutical industry, a wide range of excipients may be blended together with the active pharmaceutical ingredient to create the final blend used to manufacture the solid dosage form. The range of materials that may be blended (excipients, API), presents a number of variables which must be addressed to achieve target product quality attributes. These variables may include the particle size distribution (including aggregates or lumps of material), particle shape (spheres, rods, cubes, plates, and irregular), presence of moisture (or other volatile compounds), particle surface properties (roughness, cohesion), and powder flow properties.^[5]

Milling[edit]

During the drug manufacturing process, milling is often required in order to reduce the average particle size in a drug powder. There are a number of reasons for this, including increasing homogeneity and dosage uniformity, increasing bioavailability, and increasing the solubility of the drug compound.^[6] In some cases, repeated powder blending followed by milling is conducted to improve the manufacturability of the blends.

Granulation[edit]

In general, there are two types of granulation: wet granulation and dry granulation. Granulation can be thought of as the opposite of milling; it is the process by which small particles are bound together to form larger particles, called granules. Granulation is used for several reasons. Granulation prevents the 'demixing' of components in the mixture, by creating a granule which contains all of the components in their required proportions, improves flow characteristics of powders (because small particles do not flow well), and improves compaction properties for tablet formation.^[7]

Hot melt extrusion[edit]

Hot melt extrusion is utilized in pharmaceutical solid oral dose processing to enable delivery of drugs with poor solubility and bioavailability. Hot melt extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier increasing dissolution rates and bioavailability. The process involves the application of heat, pressure and agitation to mix materials together and 'extrude' them through a die. Twin-screw high shear extruders blend materials and simultaneously break up particles. The resulting particles can be blended and compressed into tablets or filled into capsules.^[8]

See also[edit]

References[edit]

Capsule Manufacturing Equipment

1. ^ ^abcLaird, Trevor (July 2010). 'How to Minimize Scale Up Difficulties'(PDF). Chemical Industry Digest: 51–56.
2. ^Blackshields, Caroline A.; Crean, Abina M. (2018-07-03). 'Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review'. Pharmaceutical Development and Technology. 23 (6): 554–560. doi:10.1080/10837450.2017.1339197. ISSN1083-7450. PMID28590824.
3. ^Wang, Yifan; Li, Tianyi; Muzzio, Fernando J.; Glasser, Benjamin J. (2017-02-15). 'Predicting feeder performance based on material flow properties'. Powder Technology. 308: 135–148. doi:10.1016/j.powtec.2016.12.010. ISSN0032-5910.
4. ^Cartwright, James J.; Robertson, John; D'Haene, Dorie; Burke, Matthew D.; Hennenkamp, Jeffrey R. (2013-04-01). 'Twin screw wet granulation: Loss in weight feeding of a poorly flowing active pharmaceutical ingredient'. Powder Technology. Special Issue: 5th International Granulation Workshop Granulation across the length scale 2011. 238: 116–121. doi:10.1016/j.powtec.2012.04.034. ISSN0032-5910.
5. ^Baxter, Thomas; Prescott, James (2009-01-02). Developing Solid Oral Dosage Forms. Academic Press. ISBN978-0-444-53242-8.
6. ^'Pharmaceutical Drug Formulation, Development & Drug Delivery'. Particle Sciences. Retrieved 2015-10-24.
7. ^Aulton, Michael; Malcolm, Summers (2013). Aulton's Pharmaceutics: The Design and Manufacture of Medicines. China: Churchill Livingstone Elsevier. p. 465. ISBN978-0-7020-4290-4.
8. ^'Extrusion Spheronisation'. PharmaCMC. Archived from the original on 1 October 2016. Retrieved 26 September 2016.

Pharma Capsules