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.
Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication.[citation needed] 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] 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 medication.
Single-piece gel encapsulation ("soft capsules")Edit
Soft gel capsules.Advil liqui-gels
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 the 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
Two-piece, hard starch capsulesReconstruction from µCT-data of a hard starch capsule containing Diclofenac. Resolution 18,6 µm/pixel.Flight through the image stack of the above scan.
James Murdoch 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, and the capsule is filled with powder or more normally pellets made by the process of extrusion and 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]
Gelatin capsules, informally called gel caps or gelcaps, are composed of gelatin manufactured from the collagen of animal skin or bone.[4]
Vegetable capsules, introduced in 1989,[5] are made from cellulose, a structural component in plants. The main ingredient of vegetarian capsules is hydroxypropyl methyl cellulose. In the 21st century, gelatin capsules are more broadly used than vegetarian capsules because the cost of production is lower.[citation needed]
Manufacturing equipmentEdit
The process of encapsulation of hard gelatin capsules can be done on manual, semi-automatic, and automatic capsule filling machines. Hard gelatin capsules are manufactured by the dipping method which is dipping, rotation, drying, stripping, trimming, and joining.[6] 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.[7]
Volume is measured to the fill line, which is customary to the top of the smaller-diameter body half.[citation needed] After capping, some ullage volume (air space) remains in the finished capsule.
A new class of capsules has been developed whereby drugs can be embedded in the capsule shell matrix. As these are patented by Dr. Hemant N Joshi, these new capsules are named as "Joshi Capsules". This allows different drugs to be delivered using the same capsule. The drug might be in a solubilized form, suspended form or chemically bound form in the capsule shell matrix. The drug can be in the cap of the capsule, the body of the capsule or in both body and cap of the capsule. One can embed more than one drug in the capsule shell matrix. The drug can be in the dissolved and suspended form in the capsule shell matrix. Thus, one can create various types of variations in these "drug-embedded capsules". The rate of release of drug can vary based on the way the drug is embedded in the capsule shell matrix and drug properties.[8][9]
^Safire, William (March 9, 1986). "On Language; The Caplet Solution". The New York Times. Retrieved December 6, 2017.
^"History of dosage forms and basic preparations". Encyclopedia of Pharmaceutical Technology. Vol. 7. Informa Health Care. 1998. pp. 304–306. ISBN0-8247-2806-8.
^Bill Bennett; Graham Cole (2003). Pharmaceutical Production, an Engineering Guide. IChemE. pp. 126–129. ISBN0-85295-440-9.
^Prakash, A.; Soni, H.; Mishra, A.; Sarma, P. (2017). "Are your capsules vegetarian or nonvegetarian: An ethical and scientific justification". Indian Journal of Pharmacology. 49 (5): 401–404. doi:10.4103/ijp.IJP_409_17 (inactive August 1, 2023). PMC5830853. PMID 29515283.{{cite journal}}: CS1 maint: DOI inactive as of August 2023 (link)
^Tatham KC, Patel KP (2014). "Why can't all drugs be vegetarian?" (PDF). BMJ. 348: g401. doi:10.1136/bmj.g401. PMID 24496281. S2CID 42628750.
^. PharmaCMC. Archived from the original on October 6, 2016. Retrieved September 27, 2016.
^Joshi, H.N., Tara Innovations LLC, 2014. Physically/molecularly distributed and/or chemically bound medicaments in empty, hard capsule shells. U.S. Patent 8,728,521.
^Joshi, H.N., 2018. Physically dispersed, molecularly dissolved and/or chemically bound drugs in an empty, hard capsule shell composition. U.S. Patent 9,884,024.
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.
Hemant N. Joshi, US Patent #8,728,521 (May 20, 2014).
Hemant N. Joshi, US Patent # 9,884,024 (February 6, 2018).
Hemant N. Joshi, US Patent # 10,357,461 (July 23, 2019).
Harshada Sant, MS, "Joshi Capsules" US Patent Numbers # 8,728,521 and # 9,884,024, American Pharmaceutical Review, Page 60, April 2018.
August 31, 2023
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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 Capsules Both of these classes of capsules are made from aqueous solutions of gelling agents such as animal protein 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 Since their inception capsules have been viewed by consumers as the most efficient method of taking medication citation needed 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 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 medication Contents 1 Single piece gel encapsulation soft capsules 2 Two piece gel encapsulation hard capsules 3 Manufacturing materials 4 Manufacturing equipment 5 Standard sizes of two piece capsules 6 Drug embedded empty capsule shells 7 See also 8 ReferencesSingle piece gel encapsulation soft capsules Edit Soft gel capsules Advil liqui gelsIn 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 the 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 lt 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 Two piece hard starch capsules Reconstruction from µCT data of a hard starch capsule containing Diclofenac Resolution 18 6 µm pixel source source source source source source source source source source source source source source source Flight through the image stack of the above scan James Murdoch 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 and the capsule is filled with powder or more normally pellets made by the process of extrusion and 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 ingredients and any excipients such as binders disintegrants fillers glidant and preservatives Manufacturing materials EditGelatin capsules informally called gel caps or gelcaps are composed of gelatin manufactured from the collagen of animal skin or bone 4 Vegetable capsules introduced in 1989 5 are made from cellulose a structural component in plants The main ingredient of vegetarian capsules is hydroxypropyl methyl cellulose In the 21st century gelatin capsules are more broadly used than vegetarian capsules because the cost of production is lower citation needed Manufacturing equipment EditThe process of encapsulation of hard gelatin capsules can be done on manual semi automatic and automatic capsule filling machines Hard gelatin capsules are manufactured by the dipping method which is dipping rotation drying stripping trimming and joining 6 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 7 Volume is measured to the fill line which is customary to the top of the smaller diameter body half citation needed After capping some ullage volume air space remains in the finished capsule Standard sizes of two piece capsules EditSize Volume mL A Locked length mm A External diameter mm A 5 0 13 11 1 4 914 0 20 14 3 5 313 0 27 15 9 5 822 0 37 18 6 351 0 48 19 4 6 910 0 67 21 7 7 650E 0 7 23 1 7 6500 0 95 23 3 8 53000 1 36 26 14 9 9113 3 2 30 15 312 5 40 5 15 312el 7 5 57 15 511 10 47 5 20 910 18 64 23 47 24 78 23 4Su07 28 88 5 23 4A ApproximateDrug embedded empty capsule shells EditA new class of capsules has been developed whereby drugs can be embedded in the capsule shell matrix As these are patented by Dr Hemant N Joshi these new capsules are named as Joshi Capsules This allows different drugs to be delivered using the same capsule The drug might be in a solubilized form suspended form or chemically bound form in the capsule shell matrix The drug can be in the cap of the capsule the body of the capsule or in both body and cap of the capsule One can embed more than one drug in the capsule shell matrix The drug can be in the dissolved and suspended form in the capsule shell matrix Thus one can create various types of variations in these drug embedded capsules The rate of release of drug can vary based on the way the drug is embedded in the capsule shell matrix and drug properties 8 9 See also EditCapsule endoscopy OROS Pharmacy Automation The Tablet Counter Pharmaceutical formulation Pill splitting Tablet OblaatReferences Edit Safire William March 9 1986 On Language The Caplet Solution The New York Times Retrieved December 6 2017 History of dosage forms and basic preparations Encyclopedia of Pharmaceutical Technology Vol 7 Informa Health Care 1998 pp 304 306 ISBN 0 8247 2806 8 Bill Bennett Graham Cole 2003 Pharmaceutical Production an Engineering Guide IChemE pp 126 129 ISBN 0 85295 440 9 Prakash A Soni H Mishra A Sarma P 2017 Are your capsules vegetarian or nonvegetarian An ethical and scientific justification Indian Journal of Pharmacology 49 5 401 404 doi 10 4103 ijp IJP 409 17 inactive August 1 2023 PMC 5830853 PMID 29515283 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of August 2023 link Tatham KC Patel KP 2014 Why can t all drugs be vegetarian PDF BMJ 348 g401 doi 10 1136 bmj g401 PMID 24496281 S2CID 42628750 Bhakar Naresh December 28 2020 Capsules Types and formulation Complete guide Pharmaguddu Pharmaguddu Pharmaceutical Encapsulation PharmaCMC Archived from the original on October 6 2016 Retrieved September 27 2016 Joshi H N Tara Innovations LLC 2014 Physically molecularly distributed and or chemically bound medicaments in empty hard capsule shells U S Patent 8 728 521 Joshi H N 2018 Physically dispersed molecularly dissolved and or chemically bound drugs in an empty hard capsule shell composition U S Patent 9 884 024 L Lachman H A Lieberman J L Kanig 1986 The Theory and Practice of Industrial Pharmacy Third ed Lea amp Febiger Philadelphia ISBN 0 8121 0977 5 Hemant N Joshi US Patent 8 728 521 May 20 2014 Hemant N Joshi US Patent 9 884 024 February 6 2018 Hemant N Joshi US Patent 10 357 461 July 23 2019 Harshada Sant MS Joshi Capsules US Patent Numbers 8 728 521 and 9 884 024 American Pharmaceutical Review Page 60 April 2018 Retrieved from https en wikipedia org w index php title Capsule pharmacy amp oldid 1168216147, wikipedia, wiki, book, books, library,
