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SEMINAR ON MODIFIED RELEASE CAPSULES

PRESENTED BY:KRUNAL.D.SAMEJAM.PHARM SEM-2C.U.SHAH COLLEGE OF PHARMACY & RESEARCH,WADHWAN.

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LIST OF CONTENTS Introduction Innovations in capsule

o Innovations in capsule shello Innovations in capsule

system Capsule liquid and semisolid

filled Technology Chewable Soft Gelatin Capsule Recent Technology in Capsule Research article Study questions References

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INTRODUCTION(1)

Early 19th century, Mathes developed the first capsule dosage form from gelatin.

Since then this technology has been continuously improved and refined, yielding range of capsule forms available today.

Capsules are gelatin shells filled with the ingredients that make up an individual dose.

Capsules account for about 20% of all prescriptions dispensed.

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THERE ARE MAINLY TWO TYPES(2,3)(conventional)

Demerits of conventional capsules:• They are temperature & moisture sensitive.• They can be easily tempered. • Possibility of microbial growth.• Aqueous or hydroalcoholic liquids can not be

enclosed, because its dissolves the gelatin.

• Hard gelatin capsule• Soft gelatin capsule

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• Reactivity with filled component.• crosslinking reaction which occurs under

accelerated storage conditions (e.g. 40 ◦C/75%RH) consequently, disintegration of the capsule shell as well as the drug release is retarded.

• As a naturally occurring protein, gelatin is susceptible to hydrolysis to release amino acids and is inherently reactive toward many substances including aldehydes, reducing sugars, metal ions, plasticizers and preservatives.

• Gelatine for capsules is mainly of bovine origin, which creates a theoretical risk of transmitting bovine spongiform encephalopathy (BSE) via capsules.

 

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Figure 1. Relative Humidity (RH), Gelatin Moisture Content, and Hard Gelatin Capsule Properties

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Capsules are use for filling different materials likeThis design allows the filling of different types of formulation such as:

Powder Granules Beads

PastesCapletsTablets

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Objectives of modified Release capsules

Overcome the disadvantages associated with conventional capsules.

Achieve modified drug release. Encapsulation of various kind of material. Modified applications

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Modified release capsules vs conventional Capsules

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INNOVATIONS IN CAPSULE

INNOVATIONS IN SHELL INNOVATIONS IN SYSTEM SOME RECENT

TECHNOLOGIES

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INNOVATION IN CAPSULE SHELL

It includes: 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

with capsule shell

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INNOVATIONS IN CAPSULE SHELLS:• Non animal Capsule HPMC Capsules Pullulan Capsules PVA Capsule Starch Capsule

• Animal Capsule Gelatine/ PEG Capsules Coni-Snap®

Capsule(OceanCaps) Press-fit® Gelcaps LiCaps® Posilock

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1.Non-animal capsule shellA. HPMC CAPSULES(HYPROMELLOSE) (4,5,6):• Hypromellose is a release controlling polymer

with diffusion and erosion controlled release

Features :• Chemically stable.• Low moisture content than Gelatin capsule,

Less brittle • Fast dissolution • Lower water vapor permeability than Gelatin

capsule. (Gelatin>PEG-Gelatin>HPMC)• High tolerance to temperature • Chemical inactivity

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Some important comparative parameters between HPMC (Quali V) capsule and HCG are as follows (5,6):

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Brittleness test of capsules

Pressure resistant test b) hardness test in capsules 

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Rate of water vapour permeability in various capsule shells

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Oesophageal sticking tendency of Gelatin and HPMC capsule (7):

(European Journal of Pharmaceutical Sciences 15 (2002) 479–488)

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QUALI-V(7)• QUALI-V was developed by Shionogi Qualicaps. It is the first HPMC capsule

developed for eventual use in pharmaceutical products.5

.The features of QUALI-V are summarized as following:

Low moisture content Low water vapor permeability Less brittle even in low humidity Fast dissolution Low static electricity 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.

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Capsule material HPMC Gelatine

Moisture content 2-5% 13-15%

Water vapour permeability Low moderate

Substrate for protease No Yes

Maillard reaction with drug fill No Yes

Deformation by heat > 80°C > 60°C

Water dissolution at room temperature Soluble Insoluble

Static Low High

Light degradation No Possible

Comparison with gelatin capsule:

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QUALI-V®-I(8)

QUALI-V®-I: A New Key for Dry Powder Inhalers (DPI)

• Superior physical performance a moisture content.

• Content could easily arises in the usage of DPI with capsules.

• Better cutting & puncturing performance.• Excellent microbiological property.• Higher weight specifications available if

required.

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Comparison of dissolution profiles of Quali V and hard Gelatin capsules

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Drug filled in Hard gelatin capsule

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VCaps Plus® (4,6)

VCaps Plus® (HPMC Shell 2), was developed by Capsugel and introduced in 2006.

Rather than relying on a gelling agent, the new hypromellose capsule is made by a thermal gelling process using a hot-dip method.

The process consists of dipping a pre-heated capsule forming pin into an HPMC water solution maintained at a temperature below the gel point temperature, withdrawing the pins and placing the pins in ovens at temperatures above the gelation temperature, and drying the film.

HPMC gels on the surface of the heated pins and, as the pins are withdrawn, a HPMC film of a certain thickness is formed on the pins, and capsules are obtained after drying.

 Advantages: Better Physical and mechanical stability. Better disintegration and dissolution.

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Pullulan is a neutral glucan (like Amylose, Dextran,Cellulose)

Water-soluble polysaccharide • Derived by bacterial fermentation from corn.(Aureobasidium pullulans)• odorless, tasteless, and completely biodegradable .• 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.

PULLULAN CAPSULE(9)

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Merit:Pullulan capsules are known for their high oxygen impermeability, this is particularly advantageous because this means Pullulan capsules are very essential in the encapsulation of product that is sensitive to oxidation. Demerit: Depending on biosynthesis and purification procedure, a pullulan product may contain hetero polysaccharides or acid polysaccharides as impurities.

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Plantcaps™ Recently Capsugel Launched Plantcaps™ Capsules, a More Natural

Alternative Pullulan Capsule. (March 9, 2012)

“Plantcaps presents all the benefits of a gelatin capsule, but in a vegetarian form,” 

high quality pullulan to offer robust performance with a wide range of ingredients.

disintegration/dissolution profile equal to gelatin  In addition, its shell can also help eliminate

“spotting” concerns that occur when Vitamin C is encapsulated in gelatin.

Pullulan offers the best oxygen barrier of all available plant-based products, Plantcaps can even help mask pungent tastes and odors from some ingredients such as garlic.

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NP CapsTM(9) Made up of pullalan.

Pullulan is very stable and well-characterized, and has achieved wide regulatory acceptance with its proven safety record.

It’s capsules are particularly useful for the filling of oxygen sensitive product such as fish & vegetable.

Its generally use for those people who are diabetics and patients with restricted diets.

It is 100% natural they are Vegetable origin, No chemical modification, Starch-free, Preservative-free, Gluten-free.

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PVA CAPSULE(11)

PONDAC Capsule (name)

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.

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

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STARCH CAPSULE(13,14) Made from potato starch and represent a

direct alternative to hard gelatin capsule.

Manufactured by the injection moulding technique developed by Capsugel (Capill®).

Offers advantages like.◦pH independent dissolution◦Suitable for enteric coating◦Tamper evident◦Produced from non-animal derived

ingredients

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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 mold.

Officially recognized in USP 23 and NF 18

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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.

Eg. TARGIT®

ENTERIC COATED STARCH CAPSULE(15)

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Scintigraphic images of a radiolabelled TARGIT® capsule in ahuman following oral administration.

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V Caps®(16)

Two-piece capsules made from cellulosic raw materials that satisfy vegetarian and cultural needs

easy to swallow effectively mask taste and odor allow product visibility Vcaps capsules are also starch-free, gluten-free

and preservative-free, and meet the strict dietary needs of customers that choose a vegetarian lifestyle.

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ANIMAL CAPSULES

GELATIN/ PEG CAPSULES Reduce the brittleness of standard gelatin

capsules when exposed to a low-moisture content thus making the capsules more compatible to hygroscopic formulations or moisture-sensitive ingredients

Gelatin/PEG Features Less brittle Good for hygroscopic formulations Good for moisture-sensitive ingredients Odorless, tasteless Three-year shelf life Available in sizes from 00 to 4

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The addition of PEG improves the mechanical strength of the capsule.

At moisture contents between 8% - 12%, gelatin/PEG capsules have equivalent mechanical strength to standard gelatin capsules with moisture between 13% - 16%.

Gelatin/PEG capsules are available in commercial pharmaceutical productsCardiovascular (Tocopherol nicotinate) Vasodilators (Nifedipine) Antihypertensive (Captopril) Digestive Enzyme

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OceanCapsTM (17) 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, 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

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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.

PRESS-FIT® GELCAPS(18)

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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.

Manufactured by exclusive cold- shrink process on a special filling and coating machine.

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LICAPS®(1

9) 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.

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POSILOK®(20).

• It 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

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INNOVATION IN CAPSULE SYSTEMS

To provide modified release• PORT CAPSULE TECHNOLOGY• HYDROPHILIC SANDWICH (HS) CAPSULE• L-OROS®• PULSINCAP• CHEWABLE SOFT GELATIN CAPSULE

ENCAPSULATING LIQUID FILL• INNERCAP TECHNOLOGY• GALACTICLES

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PORT CAPSULE TECHNOLOGY(21)

eg. Delayed Release Pseudoephedrine

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HYDROPHILIC SANDWICH (HS) CAPSULE(22)

Simple and time delayed probe capsule

Based on a capsule within a capsule, in which the inter capsular space was filled with a layer of hydrophilic polymer (HPMC).

This effectively created a “ Hydrophilic Sandwich “ between two gelatin capsule

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GELATIN OUTER LAYER

HPMC LAYER INNER LAYER

Outer layer get dissolved

Hpmc layer swells

Release of drug from swelled hpmc gels

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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

The time delay was controlled by

◦ Molecular weight of polymer ◦ Inclusion of a soluble filler ◦ eg. Lactose

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L-OROS®(23)

For Controlled Release of Non-Aqueous Liquid Formulations

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 ◦Advantages:

Enhanced bioavailability of class II drugs Uniform blood levels over specific period of time Reduced first pass effect Reduced dose Patient compliance Made of pharmaceutical acceptable excipient

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L – ORAS HARD CAP

SEMIPERMIABLE MEMBRANE

PUSH LAYERBARRERLAYER

LIQUID DRUG FORMULATION

DELIVERY ORIFICE

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L- OROS SOFTCAPTM

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DELAYED LIQUID BOLUS SYSTEM

Delayed Liquid Bolus System

Semi permeable membraneSub coatDelay layerLiquid drug formulationOsmotic layerDelivery orifice

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PULSINCAP(24,25) Pulsincap is the pulsatile release of therapeutic agents

like preprogrammed delivery of drug at a predetermined time or in pulses of known sequence or the production of system that responds to specific stimuli.

First concept : 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.

A swelling agent mixed with the drug, was filled into the internal cavity of capsule body and a plug was used to seal the contents into the internal cavity.

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PERMEABLE CROSS LINKED HYDROGEL

DRUG FORMULATION

PLUG, CROSS LINKED HYDROGEL

SWELLING AGENTS

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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.

SECOND CONCEPT

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THIRD CONCEPT 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.

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Capsule liquid and semisolid filled Technology

Advantages of liquid- and semisolid-filled hard gelatin capsules include:

• Improved bioavailability• Improved content uniformity of low-dose active

substances• Reduced dust for handling potent compounds• Process simplification for low-melting-point active

substances• Enhanced stability• Sustained release

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Drug Characteristics and Liquid-filling Technologies

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Chewable Soft Gelatin Capsule(3,26)

A chewable, edible soft gelatin capsule which comprises:

(a) a soft gelatin shell which comprises: about 20-45% gelatin; about 15-30% water; about 17.5-35% plasticizer; and about 5-25% hydrogenated starch hydrolysate; and wherein said shell encloses

(b) a soft gelatin capsule fill material.• 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 Placticizers Water Moisture retaining agent Other

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Recent Technology in Capsule

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DuoCapTM(27)

DuoCapTM, 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.

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INNER CAP TECHNOLOGY(28)

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.

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The combination dosage form consists of a primary HPMC capsule containing an emulsion,pH coated tablet,crystalline filled HPMC capsule and abeadlet filled gelatin capsule.

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Opportunities offered by Multi – Phase Multi-compartment

CapsulesMulti -Phased MaterialsIncompatible Drugs in Single DosageCapsule Shell MaterialsMultiple Release ProfilesSingle TherapiesMultiple TherapiesEase of Scale-UpLess ExcipientIncreased Bioavailability Through AbsorptionIncreased Stability

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ORBEXA® TECHNOLOGY(29)

It produces beads that are of controlled size and density and suitable for formulation as controlled release multiparticulates - using granulation, spheronization and extrusion technique.

• The resultant beads can be coated with functional polymer membrane for additional release rate control and may be filled into capsules

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Advantages of Orbexa• Aqueous or solvent-based

granulation.• High-speed process is well suited

for sensitive molecules like proteins.

• Suitable for high drug loading.

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SODAS® Technology(30)

• SODAS® (Spheroidal Oral Drug Absorption System) is particulate drug delivery system.

• SODAS® Technology is based on the production of uniform spherical beads of 1-2mm in diameter containing drug plus excipients and coated with product specific controlled release polymers.

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CODAS® TECHNOLOGY(31)

• Chronotherapeutic Oral Drug Absorption System(CODASTM Technology) was developed to achieve prolonged interval.

• 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.

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• 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.

• The water insoluble polymer continues to act as a barrier, maintaining the controlled release of the drug.

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5. PRODAS® TECHNOLOGY(32)

• which is unique in that it combines the benefits of tabletting technology within a capsule.

• It can be used to pre-program the release rate of a drug.

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• PRODAS® technology, by incorporating minitablets with different release rates, can display the characteristics of a number of different conventional dosage forms:

• delayed release component for site/regional release and/or food resistance

• sustained release component for additional controlled release/profile extension

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Banner’s VersetrolTM Technology(33)

• Novel innovative Technology that provides time controlled release for wide range of drug.

• Drug is incorporated in lipophilic or hydrophilic matrix and that is than incorporated in soft gelatin capsule shell.

• Technology is versatile because depending on physicochemical property of drug either emulsion/suspension can be developed.

• For lipophilic drugs suspension formulation is preferred while for hydrophilic drugs emulsion form is utilized. By applying combination of lipophilic and hydrophilic matrices desire release profile can be achieved.

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Bijel Capsules: Co-release Micro-gel

New generic route to gel capsule formulation, involving particles suspended in fluid-bicontinuous mixture of two solvents.

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• The bijel capsules are made of two fluids and hence they are both a gel and an emulsion.

• The water and oil domains inside the capsules can be used to deliver chemically different active ingredients.

• The capsules can be designed to release or mix the active ingredients in response to a specific external stimulus.

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Galacticles™(34) 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

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•Potential for Improved Drug Absorptionimprove oral bioavailability for hydrophilic and

lipophilic drugs with low solubility. •Potential for Reduced Degradation in the GI Tract reduce degradation as well as improve absorption may be especially useful for drugs, for which both low solubility and degradation in

the GI tract contribute to a low oral bioavailability

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•Tolerability & TasteIt is less prone to cause irritation The favorable taste of Galacticles™

formulations compared to corresponding formulations with phospholipids and synthetic surfactants.

•SafetyThe components of Galacticles™ are natural

dietary lipid components found in processed and natural foods.

Preliminary safety studies indicate no toxic effects of oral administration

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     1st Generation 2nd Generation 3rd Generation 4th Generation 5th Generation

Structure

Concept

2 layers capsules

Development of encapsulator

Reduction of shell ratio

3 layers capsules

Encapsulate hydrophilic

substances Mass production

3 layers capsules

Development of acid resistance

shell Application to ethical drugs

4 layers capsules

Control of release

Development of Biocapsule

Incubation and cultivation in

capsule

Development

of function

Improve stability of content

Encapsulate liquid

Mixture with products

Burst impact

DDSImprovement of

compliance

Deepen DDSFunctional

Development of 4 layers capsules

Semipermeablemembrane

Biotechnology

Shell Function Solubility

Freezing resistance

Heat resistanceAcid resistance

Control of release

Solution in mouth+

Solution in stomach

    Control of release

Semipermeable membrane

Content FlavorFunctional oil

Hydrophilic flavorFruit juice exstract

Hydrophilic substance

Bifidus powderFunctional oil

LactobacillusYeast

DNA. cell

CategoryFood

Quasi-drugCosmetics

FoodQuasi-drugCosmetics

FoodQuasi-drugCosmetics

Drug

FoodDrug

Biotechnology area

Application

Chewing gumHealth foodTooth paste

Instant noodle

Crystal DewCapsule JINTAN

Ice cream

BifinaConstipation OTC

SolmiranTwin clean

Plum Freshener Biotechnology

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SOME MARKETED PREPARATIONS

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Mukesh C. Gohel*, Manhapra Sumitra G.Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, Ahmedabad 380 009, Gujarat, India

Research article

Modulation of active pharmaceutical material release from a novel ‘tablet in capsule system’

containing an effervescent blend

Journal of Controlled Release 79 (2002) 157–164

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In this study, an attempt was made to develop and evaluate a formulation analogous to the Pulsincap TM system consisting of an impermeable capsule body and a swellable / erodible plug.

The effect of various parameters such as type of plug materials, plug weight and capsule content were investigated in order to characterize the lag time and the drug release profiles. Diltiazem HCl was chosen as a model active pharmaceutical material.

The objective of this study was to develop a dosage form which releases the drug with a lag time of 4 h and a fast drug release thereafter.

The lag time is defined as the time until 10% of drug has been released.

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Batch Weight of Weight of effervescent blend Weight  HPMC K15M (NaHCO 3 :citric acid, 1:1) of DCP  (mg) (mg) (mg)         

A1 150 – 135  A2 100 – 185  A3 85 – 200  A4 70 – 215  A5 55 – 230  B1 90 0 195  B2 90 50 145  B3 90 75 120  B4 90 100 95           

Table 1 Composition of various batches using powder plugs

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Table 2      Composition of various batches using

tablet plugs    

Batch Composition of plug WeightAmount of

effervescent blend    of plug (NaHCO 3 :citric acid, 1:1)    (mg) (mg)

C1 HPMC K15M 150 –C2 HPMC K15M 200 –C3 HPMC 20 cPs 150 –C4 HPMC 20 cPs 200 –D1 HPMC K15M, 10% w / w NaCl 200 –D2 HPMC K15M, 20% w / w NaCl 200 –D3 HPMC K15M, 30% w / w NaCl 200 –E1 HPMC K15M:lactose, 1:1 200 –E2 HPMC K15M:lactose, 1:2 200 –E3 HPMC 20 cPs:lactose, 1:2 200 –E4 HPMC 20 cPs:lactose, 1:2 200 –F1 HPMC K15M 200 35F2 HPMC K15M 200 50F3 HPMC K15M 150 35F4 HPMC K15M 150 50

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Results and discussion

1. Powder plugsWith a plug (HPMC K15M) weight of 150 mg (Batch A1),

less than 10% of the drug was released in 4 h. Though the lag time criterion was satisfied, the release of the drug there after was in a delayed fashion (less than 20% in 8 h).

The drug release was found to be inversely proportional to the weight of the plug. A linear relationship was observed between weight of the plug and log percentage drug release in 4 h

1.1. Effect of plug weight

Lag time criterion was not satisfied by the capsules containing 70 (Batch A4) and 55 mg (Batch A5) HPMC K15M, respectively.

Less than 10% of the drug was released in 4 h from formula tions containing 100 mg (Batch A2) and 85 mg (Batch A3) HPMC K15M. The drug release was gradual after 4 h.

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1.2. Effect of effervescent baseIn the case of the formulation containing 75 mg

(Batch B3) of the effervescent blend, the drug release could be con-trolled to nearly 10% in the initial 4 h followed by almost total drug release in the next 4 h

The formulation containing 100 mg (Batch B3) of effervescent base showed almost total drug release in 5 h but with a lag time of 3 h. This formulation failed to meet the selection criterion of less than 10% drug release in 4 h (24% drug release was observed from the batch).

Based on this study, it may be concluded that the formulation containing 75 mg of effervescent blend is a good candidate for obtaining pulsatile drug release.

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2. Tablet plug

After a lag time (4 h), the drug was released in an extended fashion and not in a pulsatile fashion (Batches C1–C4)

2.1. Effect of addition of electrolytes

An attempt was made to incorporate NaCl as an electrolyte into the HPMC K15M plug to reduce its swelling so that the plug would be easily ejected.

The expected change in drug release was also not noticed. The % drug release was 22, 23, 26 and 29% after 8 h from capsules containing 0, 10 (Batch D1), 20 (Batch D2) and 30% (Batch D3) NaCl, respectively.

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2.3. Effect of effervescent baseFormulations containing 35 (Batch F1)

and 50 mg (Batch F2) of the effervescent base and having a plug weight of 200 mg passed the set criteria of lag time as well as fraction of drug released within the lag time. These formulations also showed a burst release of the drug after the lag time. However, the formulation containing 35 mg of effervescent base was considered as the best candidate for obtaining the required pulsatile drug release as this formulation best matched the fixed criteria

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A tablet-in-capsule pulsatile drug delivery system containing a water soluble drug, diltiazem HCl, for oral use was developed using a plug of HPMC in a water insoluble capsule body. The formulation factors affecting the drug release pattern were investigated. The lag time and the drug release rate thereafter can be modulated by making changes in the formulation of plug and the fill material. Immediate drug release, after a lag time of 4 h, can be obtained if the plug is pushed off by the CO 2 gas generated by interaction of NaHCO 3 and citric acid. On the other hand, slow drug release was observed from the swollen unejected plug. The use of effervescent blend has not been explored by researchers for obtaining pulsatile drug release in the earlier studies. It is concluded that programmed drug delivery can be obtained by systemic formulation approach.

Conclusion

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GTU QUESTIONS

1. Short note on Non animal capsules shells (Remedial dec’10)

2. Enlist vegetable capsule. Explain significance of pullulan capsule (Dec-2011)

3. Enlist recent innovation in advances in capsules. Describe any one in detail. (July-2010)

4. Write a note on Pulsincape Technology. (Dec-2011)

5. Discuss in detail the recent innovations in capsule tech. (June/july’11)

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REFERENCES

1. Jones, B.E. Pharmaceutical Capsules, 2nd Ed.; Podczeck, F., Jones, B.E., Eds.; Pharmaceutical Press: London, 2004. Chapters 1, 3, 4 and 13.

2. Encyclopedia of pharmaceitucal technology, 3rd edition; vol. 3; James Swarbrcik. Page no. 406.

3. Stanley, J.P. Soft gelatin capsules. In The Theory and Practice of Industrial Pharmacy, 2nd Ed.; Lachman, L., Lieberman, H.A., Kanig, J.L., Eds.; Lea Febiger: Philadelphia, 1976; 359.

4. M. Sherry Kua, Qinghong Lua,, Weiyi Li b, Yansong Chena; Performance qualification of a new hypromellose capsule: Part II. Disintegration and dissolution comparison between two types of hypromellose capsules.

5. http://www.drugdeliverytech.com/ Advantages to HPMC Capsules: A New Generation's capsule technology, issue Date: Vol. 2 No. 2 March/April 2002, Posted On: 3/28/2008

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6. M. Sherry Ku et al; Performance qualification of a new hypromellose capsule: Part II. Disintegration and dissolution comparison between two types of hypromellose capsules.International journal of pharmaceutics. www.elsevier.com/locate/ijpharm

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Dry Powder Inhalers , Issue Date: Vol. 3 No. 6 September 2003, Posted On: 3/28/2008

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10. http://capsugel.com/en/products-services/products/capsules/plantcaps/

11. www.nisshinkasei.co.jp/ english/development/pondac12. Vinod D. Vilivalam, Lisbeth Illum and Khurshid Iqbal; Starch

capsules: an alternative system for oral drug delivery, Pharmaceutical Science & Technology Today. Volume 3, Issue 2, 1 February 2000, Pages 64–69

13. S.J. Burns, D. Corness, G. Hay, S. Higginbottom, I. Whelan, D. Attwood, S.G. Barnwell

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14. An in vitro assessment of liquid-filled capill® potato starch capsules with biphasic release characteristics . International Journal of Pharmaceutics, Volume 134, Issues 1–2, 28 May 1996, Pages 223-230.

15. Anna Dimantov, Menahem Greenberg, Ellina Kesselman, Eyal Shimoni; Study of high amylose corn starch as food grade enteric coating in a microcapsule model system , Innovative Food Science & Emerging Technologies, Volume 5, Issue 1, March 2004, Pages 93-100

16. www.vegetariancapsules.com/non_animal_vcaps.php17. www.capsugel.com/products/ocean/php18. http://www.pharmaceuticalonline.com/doc.mvc/Press-Fit-Gelcap

s-000119. http://vitaslim.eu/en/licaps-by-capsugel/page/14620. http://www.comintermexico.com/Qualicapsl.htm21. www.porttechnology.com 22. Stevens HNE, Ross, AC, Johnson JR. The hydrophilic sandwich

capsule: a convenient time delayed oral probe device. J pharm Pharmacol 52:S41, 2000.

23. http://www.drugdeliverytech.com/ L-OROS® SOFTCAPTM for Controlled Release of Non-Aqueous Liquid Formulations Issue Date: Vol. 2 No. 1 January/February 2002, Posted On: 3/28/2008

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24. T. Bussemer, A. Dashevsky, R. Bodmeier; A pulsatile drug delivery system based on rupturable coated hard gelatin capsules. Journal of Controlled Release 93 (2003) 331– 339

25. Burns JS, Stevens HNE, McEwen J, Pritchard G, Brewer FM, Clarke A, Johnsons ES, McMillan IJ. Control. Release, 1996, 38, 151.

26. Bentley’s Text book of Pharmaceutics, eighth edition Encyclopedia of Pharmaceutical Technology, edited by James Swarbrick, third edition Volume I.

27. http://www.encapdrugdelivery.com/news-and-events/articles/encap-drug-delivery-receives-patent-approval-for-duocap-capsule-system1

28. http://www.innercap.com/29. Deepika Jain,1 Richa Raturi,2 Vikas Jain,1,* Praveen Bansal3 and

Ranjit Singh2,Recent technologies in pulsatile drug delivery systems. Landes Bioscience July/August/ september 2011; © 2011

30. www.elandrugtechnologies.com/oral_controlled_release/sodas31. www.elandrugtechnologies.com/oral_controlled_release/codas32. www.elandrugtechnologies.com/oral_controlled_release/prodas33. PharmaBioWorld, October2009,Vol8,Issue 3;71-77.34. GalacticlesTM Oral Lipid Matrix in Liquid-Filled Softgel Capsules: A

Novel Drug Delivery System for Improved Oral Bioavailability. Issue Date: Vol. 2 No. 7 October 2002, Posted On: 3/28/2008 http://www.drugdeliverytech.com/

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Thank you……….