Modified Release Capsules

Modified Release CapsulesN o v e l D r u g D e l I v e r y S y s t e m - I

Asst. ProfessorDepartment of PharmaceuticsShree Swaminarayan Sanskar

Pharmacy College, Zundal

Roll No:15MPharm Sem- II

Department of PharmaceuticsShree Swaminarayan Sanskar

Pharmacy College, Zundal

Guided By:

Bhavna A. Patel

Presented By:

Vatsal R. Patel

2Department of Pharmaceutics, SSPC, Zundal

List of Contents

IntroductionInnovations Related to Capsule Shells

1

2

Innovations in Capsule Fill Material

3

Innovations in Capsule System4

References5

HPMC Capsule Starch Capsule PVA Capsule Chitosan Capsule Cross linked Dextran Capsule


List of Contents


1

2


3


References5


List of Contents


1

2


3


References5

Pulsincap Hydrophilic Sandwich (Hs) Capsule L-Oros System Port System Targeting Lymphatic Delivery Fast Disintegrating Capsules


List of Contents


1

2


3


References5


Modified Release Capsules

Introduction1

• Capsules are dosage forms in which unit doses of powder, semisolid, or liquid drugs are enclosed within either a hard or a soft envelope or shell.

• Administration route of capsules: orally (whole or mixed with food or drink after opening capsules)



Introduction1

• In early 19th century, Mathes developed the first capsule dosage form from gelatin.

• Since then this technology has been continuously improved and refined in terms of capsule shell, formulation and system, yielding range of capsule forms available today.

• Capsules account for about 20% of all prescriptions dispensed



Why need of Innovations in Capsule ?

1.1

• Overcome the disadvantages associated with conventional capsules

• Achieve modified drug release

• Encapsulation of various kind of materials

• Modified applications



Innovations related to Capsule Shells

2

• Alternatives to Gelatin

• Gelatine/ PEG Capsules

• Coni-Snap ® • Press-fit ®

Gelcaps • LiCaps ®• Posilock • Minicasule • Dbcaps ®

Capsules

• HPMC Capsules• Pullulan Capsules• PVA Capsule• Starch Capsule• V Caps ®

Non-Animal Capsule ShellsA

Animal Capsule ShellsB

Ideal Requirements




2

Good Film Property

FastDissolution

at 37°C

Good Gelation Property

for Casting

Low Toxicity

Compatibility with existing Machinery

Possible Innovations




2

Improvement in the shell property

Provide physical strength

Protection from moisture

Protection from microbial contamination

Protection from light and oxygen

Improve compatibility of fill material



• QUALI-V, developed by Shionogi Qualicaps, is the first HPMC capsule developed for eventual use in pharmaceutical products.

FEATURES

• Made from non-animal materials,• Chemically stable.• Low moisture content than Gelatin capsule, as determined by

Microbalance system.• Less brittle even in low humidity(≤1% moisture content)• Fast dissolution (No change in dissolution profile under stress conditions)

and soluble in water at room temperature.

HPMC Capsule Shells (Hypromellose)


2



• No cross linking• Lower water vapor permeability than Gelatin capsule.(Gelatin>PEG-

Gelatin>HPMC)• Low static electricity and light protected.• No Maillard reaction with fillings.• High tolerance to temperature • Chemical inactivity and solubility at room temperature.• In these type of capsules powder, tablet, granules, pellets, liquids and

semisolids are filled.• Suited to automatic capsule filling machines.

HPMC Capsule Shells (Hypromellose)


2



HPMC Quali-V Vs Gelatin


2



• Water-soluble polysaccharide • Derived by bacterial fermentation from corn• They are odorless, tasteless, and completely biodegradable • Used in production of foods, pharmaceuticals and cosmetics. • The film formation properties of Pullulan are similar to gelatin.• Dried capsules are comparatively weak in physical strength.• Requires water to act as a film plasticizer, which may have a negative

effect on active ingredients. • Only one supplier of the raw material• Does not show any meaningful advantages over hypromellose

Pullulan Capsule Shells


2



• Made up of pullalan• Pullulan is very stable and well-characterized, and has achieved wide

regulatory acceptance with its proven safety record. • Its generally use for those people who are vegetarians, diabetics and

patients with restricted diets.• It is 100% natural they are Vegetable origin, No chemical modification,

Non-GMO, Starch-free, Preservative-free, Gluten-free.

NP Caps ™ : Pullulan Capsule Shells


2



• Insoluble drugs can be dissolved in solvents such as Macrogol 400, being filled in capsules.

• The bioavailability of insoluble drugs can be improved very much. • E.g. PONDAC Capsule • The oxygen permeability of PVA copolymer capsule is significantly low. • The gelatin capsule was developed in the 19th century. • The HPMC capsule was developed in the 20th century. • The PONDAC capsule is the hope for the 21st century.

PVA Capsule Shells


2



PVA Capsule Shells


2



Manufactured by the injection molding technique developed by Capsugel (Capill ®)• Made from potato starch and represent a direct alternative to hard gelatin

capsule• Offers advantages like.

pH independent dissolution Suitable for enteric coating Tamper evidentEg: VCaps®

Starch Capsule Shells


2



• Consists cap and body; which are sealed together at the time of filling to prevent separation.

• Sealing is achieved by applying a hydro alcoholic solution to inner section of the cap, immediately prior to its being placed on to the body.

• Different size capsules are manufactured ( Number 0, 1, 2, 3, 4) by changing the mould.

• Officially recognized in USP 23 and NF 18VCaps®:• Two-piece capsules made from cellulosic raw materials • Vcaps capsules can also starch-free, gluten-free and preservative-free • Easy to swallow• Effectively mask taste & odor



2





2



ENTERIC STARCH CAPSULES:

• Overcome coating problems encounter during coating of HGC.• Coating of starch capsules appear to be less problematic because of the

smooth seal, coupled with the higher bulk density of capsules, which provide for a more uniform coating bed.

• Stability of coated starch capsule evaluated & found good• Eg. TARGIT®



2



• OceanCapsTM is fish gelatin capsules• It contain all-natural marine supplements• Its over 40% of supplement users in France, Germany and the UK• US consumers continue to move toward natural alternatives, and look for

products like marine supplements in fish capsules• Ideally suited for fish-eating vegetarians looking for fish capsules, and

marine supplements such as fish oil, DHA, EPA, salmon liver oil, shark cartilage and glucosamine.

• Perfect for the supplement needs of fish-eating vegetarians, such as iron,zinc, calcium and vitamins B2 and B12

• Certified origin from high quality, farmed fish • Preservative-free, starch-free, gluten-free

Ocean Caps™


2



• A unique dosage form consisting of a high-gloss gelatin coating that encases a caplet core.

• Press-Fit gelcaps combine the best qualities of a gelatin capsule with the density of a tablet, creating an exciting new dosage form that can be custom engineered to meet specific product performance criteria.

• The elegant, geometric shape of Press-Fit gelcaps is distinct in the marketplace.

• The high gloss finish and extensive selection of color combinations provide additional opportunities for unique trade dress and enhanced consumer recognition.

• The outside gelatin shell is taste-free, • Safe and effective utilization in oral dosage applications.

Pressfit® Gelcaps


2



• Two-piece gelatin capsules that have been specially designed to be sealed for secure containment of liquids and semi-solids.

• In combination with a liquid fill, provides an attractive and viable dosage form, particularly for poorly soluble compounds.

• The use of hot melts is also viable with Licaps, as they may be filled at temperatures up to 70° C

Licaps®


2

http://www.capsugel.com/services/rx_liquid.php



• POSILOK® is the registered trademark for the locking system used by Qualicaps.

• It ensures that the contents reach the consumer intact, and are protected at all times from external contamination.

Posilock®


2



• The amount of material needed for testing is often very small(in mg)• Qualicap’s Minicapsule (size9) provides a dependable method of delivering

the material directly into animal’s stomach with minimal waste & great flexibility in dosing & available in gelatin &HPMC option.

• Some of the essential first pre-clinical tests that examine safety and pharmacokinetic factors are carried out on rodents or guinea pigs.

• Qualicap’s Minicapsule (size 9) provides a dependable method of delivering material directly into the animal’s stomach with minimal waste.These small, size 9 capsules can be filled with small, yet precise doses.

Minicapsules


2



Minicapsules


2

CAPACITY 25 mm3

CAP LENGTH 4.3 mm +/- 0.30 mm

BODY LENGTH 7.3 mm +/- 0.30 mm

CAP DIAMETER 2.65 mm +/- 0.10 mm

BODY DIAMETER 2.40 mm +/- 0.10 mm

CLOSED JOINED LENGTH 8.40 mm +/- 0.30 mm

WEIGHT 9.5 mg +/- 2 mg



• Adding 10-90% ethanol into mixture of HPMC 20-150parts, Tween80 8.5-25vol parts, Titanium white powder 7.5-25wt parts, Talc powder 7.5-25wt parts, 2%chocolate brown solution, 7.5-25wt parts, castor oil 15-40 vol parts to obtain coating solution, regulating flow rate of coating material at 25-40°C under relative moisture of 20-60%.

• It can produce soft capsules with slower aging speed.

COATING METHOD FOR SOFT GELATIN CAPSULES WITH IMPROVED STABILITY


2

Case

Study

Chemical Abstracts | Vol. 151 | Number 13 |September 28 , 2009 | Page2156



Innovations in Capsule Fill Materials

3

• Capsules are used for filling different materials like:

- Most Widely Used- Acceptable for

most drugs

Powders Granules Beads

- Mostly Used in the case of effervescent granules

- Used for modified drug release

- Enhances the look of Capsule



• Capsules are used for filling different materials like:

- Less commonly used

- Used In special cases

Tablets Caplets Pastes

- Less commonly

used- Used In special

cases

- Used for liquid & semisolid preparations

Innovations in Capsule Fill Materials

3



PORT CAPSULE TECHNOLOGY

HYDROPHILIC SANDWICH (HS) CAPSULE

L-OROS®

PULSINCAP

CHEWABLE SOFT GELATIN CAPSULE ENCAPSULATING LIQUID FILL

INNERCAP TECHNOLOGY

GALACTICLES

Different Capsule Technologies

Innovations in Capsule Systems

4



Port Capsule Technology


4



Port Capsule Technology


4



Hydrophilic Sandwich (SH) Technology


4



• Time delayed probe capsule , This effectively created a “ Hydrophilic Sandwich “ between two gelatin capsule .

• When the outer capsule dissolved, the sandwich of HPMC formed a gel barrier layer that provided a time delay before fluid could enter the inner capsule and cause drug release

Hydrophilic Sandwich (SH) Technology


4



L-Oros®


4



• Controlled Release of Non-Aqueous Liquid Formulation• L-OROS Hard cap• L-OROS Soft cap• Delayed liquid bolus delivery system• consists of liquid drug, an osmotic engine or push layer and a semi

permeable membrane coating • The drug layer and the osmotic engine are encased in hard capsule which

is surrounded by the rate controlling semi permeable membrane.• A barrier layer composed of an inert substance separates the drug layer

from osmotic engine.• A delivery orifice is laser drilled at the opposite end of the osmotic engine

providing an outlet for the drug.

L-Oros®


4



Advantages:• Enhanced bioavailability of class II drugs• Reduced first pass effect• Reduced dose• Patient compliance• Made of pharmaceutical acceptable excipient

L-Oros®


4



L-Oros®


4



• The liquid drug formulation is encased in soft capsule. It is in turn surrounded by a barrier layer, osmotic engine, and a semi permeable membrane in order.

• A delivery orifice in drilled through semi-permeable membrane, osmotic engine and barrier layer.

• When the osmotic engine expands it compresses the soft capsule and the drug formulation is pushed out through the delivery orifice.

L-Oros®


4



Delayed Liquid Bolus System


4



• Delivers the pulse of the liquid drug.• The system consists of the placebo delay layer, a liquid drug layer, an

osmotic engine all encased by a sub coat and then surrounded by semi-permeable membrane.

• The delivery orifice is drilled on the placebo layer of the system.• When the osmotic engine expands, the placebo is released first delaying

the drug release.• Delay in drug release can be from 1-10 hours depending on the

permeability of the rate controlling membrane and the size of the placebo layer.

Delayed Liquid Bolus System


4



Innercap Technology


4

3 in 1 Cocktail



Innercap Technology


4



• The combination example consists of a high potency insoluble active in a lipid emulsion, sustained release tablet and a cocktail of two crystalline active materials.

• A combination of release profiles can be incorporated in the system.

Innercap Technology


4



Innercap Technology


4



Pulsin Cap


4

• separation of a plug form an insoluble capsule body.

• It comprised of a water permeable body prepared from a water-swellable hydrogel cross linked PEG polymer .

First Concept Second Concept Third Concept

• capsule body is made of gelatin coated with ethyl cellulose.

• In the presence of fluid, the plug swelled at a controlled rate that was independent of the nature of pH of the medium.

• Here in this approach in place of hydrogel plug, simple erodible compressed tablet is placed

• This overcomes the need for the precise dimensional tolerance between capsule and plug for sliding mechanism of the plug.



• Chewable SGC require mixture of gelatin having different bloom values. • Most preferable combination ration : 3:1 to 5:1• It contains ingredients like,

Low bloom gelatin Medium bloom gelatin Plasticizers Water Moisture retaining agent Other

Chewable Soft Gelatin Capsule Encapsulating Liquid Fill


4



Galacticles TM


4



• Oral Lipid Matrix in Liquid-Filled Softgel Capsules• A Novel Drug Delivery System for Improved Oral Bioavailability • The Galacticles™ Lipid Matrix consists of a mixture of Galactolecithin • and one or more other lipids, for example, mono-, di-, and/or tri- glycerides.

Galacticles TM


4



SODAS® Technology:

• Spheroidal Oral Drug Absorption System is Elan’s multiparticulate drug delivery system. Based on the production of controlled release beads, the SODAS®Technology is characterized by its inherent flexibility, enabling the production of customized dosage forms that respond directly to individual drug candidate needs.

• It can provide no of tailored drug release profiles, including immediate release of drug followed by sustained release to give rise to a fast onset of action, which is maintained for 24hours. Alternatively the opposite scenario can be achieved and additional option is pulsatile release.

• The most recent regulatory approvals for a SODAS® based system is the once daily oral dosage forms of AvinzaTM ,Ritalin®LA and Focalin®XR.

Newer Technologies for Pulsatile Release


4



CODAS® Technology:

• A delay of drug action may be required for different reasons. Chronotherapy is an example of when drug release may be programmed to occur after a prolonged interval following administration. Chronotherapeutic Oral Drug Absorption System(CODASTM Technology) was developed to achieve this prolonged interval.

• Verelan ® PM product using this Technology is designed to begin releasing Verapamil approximately 4-5hrs post ingestion. Delay is introduced by the level of release controlling polymer applied to the drug loaded beads. The release controlling polymer is a combination of water soluble and water insoluble polymers.

• As water from the GIT contacts the polymer coat beads, the water soluble polymer slowly dissolves and the drug diffuses through the resulting pores in the coating.



4



PRODAS® Technology:

• Programmable Oral Drug Absorption System is multiparticulate technology; it combines the benefits of tabletting technology within a capsule.

• PRODAS® system is presented as a number of minitablets combined in a hard gelatin capsule. It can be used to pre-program the release rate of a drug. It is possible to incorporate many different mini tablets, each one formulated individually and programmed to release drug at different sites within the GIT.

• It is possible to incorporate mini tablets of different sizes so that high drug loading is possible.



4



Duocap® Technology:

• This is the only patent approved dual capsule system available to the pharmaceutical and nutraceutical industry. DuoCap involves specialist liquid-filling techniques using custom-designed filling equipment that allows the insertion of a pre-filled, smaller capsule into a larger, liquid-filled capsule. The smaller, inner capsule may contain either a liquid or semi-solid formulation and, according to the formulation or product requirements, either or both capsules may be of gelatin or HPMC composition and can be coated, if necessary. DuoCapTM has been successfully commercialized by Encap and is suited for both pharmaceutical and nutraceutical use.



4




• DuoCap™ is a single oral dosage unit that comprises a capsule-in-a-capsule and offers broad therapeutic applications. The inner and outer capsules may contain the same active drug providing multiple release profiles from the dosage unit e.g. an immediate release formulation from the outer capsule and a controlled release formulation from the inner capsule. In addition to modifying the release profiles it is also possible to target the inner and outer capsule to different areas of the GI tract (small intestine or colon) using Encap’s coating expertise. Alternatively the compartments may contain different actives for use with combination therapies or actives that are incompatible in a single capsule.



4






4



Nanoparticles• A new oral delivery system has been developed using carbone nanotube and

nanocapsules. Single-walled or multi-walled carbon nanotubes are attached onto the surface and/or within the core of nanoparticles, depending on the desired mode of delivery and target loci, leading to alternative modes of therapy. Such carbon nanotube are functionalized to better target specific cells in the body, like in the gastro-intestinal (GI) tract, solid tumors in various locations and diseased cells. Therefore, this device could be used for applications such as targeted drug/DNA/cell delivery for oral and systemic therapy for cancers of the colon, breast, ovaries and conveniently modified to treat various other maladies as well. This invention has the advantage of promoting preferential interactions between the nanotubes on or in the capsule, the drug or drug-producing system contained within or on the surface of the capsule, and the tissue in vivo, which is the target of the treatment. Conventional drug delivery approaches lack this quality.



4



• The formulation of drugs into soft gelatin capsules has gained popularity throughout the past decade due to the many advantages of this dosage form. The bioavailability of hydrophobic drugs can be significantly increased when formulated into soft gelatin capsules.1,2 Many problems associated with tableting, including poor compaction and lack of content or weight uniformity, can be eliminated when a drug is incorporated into this dosage form.3 Improved stability of drugs that are highly susceptible to oxidation can be achieved when formulated into a soft gelatin capsule

ENTERIC FILM COATING OF SOFT GELATIN CAPSULES


2

Case

Study

International Journal of Pharmaceutics | Issue Date: 6 September 2003| Vol. No. 3 | Posted On: 3/28/2008



• Ultra thin multilayer capsules are attractive and stable systems capable of delivering the bioactives. Ultra thin multilayer capsules consist of polyelectrolytic materials that are formed in the presence of a template. This is achieved through layer-by-layer adsorption of oppositely charged macromolecules on to colloidal particles. Upon extraction, the resulting cavities retain affinity for the bioactives. This review considers the fabrication, of ultra thin multilayer capsules, physiochemical properties and role of ultra thin multilayer capsules within a pharmaceutical remit. Ultrathin multilayer capsules have potential for creating satisfactory drug dosage forms.

ULTRATHIN MULTILAYER CAPSULES IN DRUG DELIVERY


2

Case

Study

Year : 2007 | Volume : 69 | http://www.ijpsonline.com/ Issue : 4 | Page : 479-488



• Treatment of age-macular degeneration requires monthly intravitreal injections, which are costly and have serious risks. The objective of this study was to develop a novel intraocular implant for drug delivery. The capsule drug ring is a reservoir inserted in the lens capsule during cataract surgery, refillable and capable of delivering multiple drugs. Avastin was the drug of interest in this study. Prototypes were manufactured using polymethylmethacrylate sheets as the reservoir material, a semi-permeable membrane for controlled delivery and silicone check valves for refilling. The device showed near zero-order release kinetics and Avastin stability was investigated with accelerated temperature studies.

THE CAPSULE DRUG DEVICE: NOVEL APPROACH FOR DRUG DELIVERY TO THE EYE


2

Case

Study

Vision Research (2010)Volume: 50 | Issue: 7 | Pages: 680-685 | Mendeley



• Hard gelatin capsules, containing riboflavin-loaded poly (N-viny1–2-pyrrolidone)-polyacrylamide cylindrical hydrogels, were modified chemically by treating with an aqueous formaldehyde solution for the purpose of delayed release of drug along the gastrointestinal tract. The tdis (disintegration time) of capsules was studied as a function of concentration of formaldehyde solution and the treatment time. The dynamic release of vitamin B2 was studied as a function of crosslinking ratio of the hydrogels. The device studied seems to have potential to be used for colon-targeted drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2277–2282, 2003

CHEMICALLY TREATED HARD GELATIN CAPSULES FOR COLON-TARGETED DRUG DELIVERY: A NOVEL APPROACH


2

Case

Study

Journal of Applied Polymer Science Volume 89 | Issue 8 | pages 2277–2282 | 22 August, 2003



• To begin with, the hydroxypropyl methylcellulose capsules containing adsorbate of eutectic mixture of ibuprofen and menthol and pregelatinized starch were coated with ethyl cellulose. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2 (two hour), 6.0 (1hr), 7.2 (two hour) and 6.4 (three hour) mimicking different regions of gastrointestinal tract. The optimized batch with two per cent and 6.5% weight gain of ethyl cellulose and Eudragit; S100 showed less than eight per cent drug release in stomach and intestinal pH. The remaining 92% drug release was obtained thereafter from the optimized batch within two hours in colonic pH.

A NOVEL COLONIC DRUG DELIVERY SYSTEM OF IBUPROFEN


2

Case

Study

Asian journal of pharmaceuticsYear : 2009 | Volume : 3 | Issue : 3 | Page : 233-239



Electronic



Electronic



Electronic



Diagnostic



References5

• Pharmaceutical capsules. Second edition• www.nisshinkasei.co.jp/english/development/pondac• www.qualicaps.com/corporate.cfm• www. Drugdeliverytech.com • www.jintan.com• http://en.wikipedia.org/wiki/Encapsulation_(pharmacology)• www.capsugel.com• www.innercaps.com• Chemical Abstracts, Vol 151, Number 13, September 28,2009 ,

Page2156, 297838p• PharmaBioWorld, October2009,Vol8,Issue 3,Page71-77 • The influence of pellet shape and film coating on the filling of pellets into

hard shell capsules., European journal of pharmaceutical and bio pharmaceutics, 2006, 53(3) 327-333

http://www.innercaps.com/



References5

• The effect of shape and porosity on the compression behavior and tablet forming ability of granular materials formed from microcrystalline cellulose. European journal of pharmaceutics and bio pharmaceutics, 2005, 52, 347-357.

• Influence of process variables on physical properties of pellets using extruder spheronizer. Drug development industrial pharmacy, 25 (!) , 45-61 (1999).

• Encyclopedia of Pharmaceutical technology, Volume 11, Page no-369. • Physical characteristics of HPMC and HEC and investigation of their use

as pelletization aids, R. Catlapalli, B.D. Rohera, International Journal of Pharmaceutics, 161(1998)179-193.

• Eudragit NE40–Drug Mixed Coating System for Controlling Drug Release of Core Pellets Drug Development And Industrial Pharmacy, Taylor & Francis Issue: Volume 31 number4-5/2005 Pages: 339 - 347



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