Dispersed Systems Consist of Two Phase

8/13/2019 Dispersed Systems Consist of Two Phase

1/13

Pharmaceutical Process Design I: Synthesis, Separations and SterileProcessing Project

PHARMACEUTICAL DOSAGE FORM- SUSPENSIONS

PATEL MEERA
http://coewww.rutgers.edu/bglasser/ResearchGroup/Courses/155-545/545home.htmlhttp://coewww.rutgers.edu/bglasser/ResearchGroup/Courses/155-545/545home.htmlhttp://coewww.rutgers.edu/bglasser/ResearchGroup/Courses/155-545/545home.htmlhttp://coewww.rutgers.edu/bglasser/ResearchGroup/Courses/155-545/545home.html


2/13

PHARMACEUTICAL DOSAGE FORMS: SUSPENSIONS

Table of Contents

1. Introduction

2. Reasons for the Pharmaceutical Suspensions

3. Classification of the Pharmaceutical Suspensions

4. Features of an Ideal Suspension

5. Important factors to be considered in formulation of the Suspensions

6. Aerosols

7. Advantages of the aerosols

8. Pharmaceutical Aerosols

9. Meter-dosed Inhaler (MDI)

10. Proper administration and usage of the aerosol

11. Summary

12. References


3/13


INTRODUCTIONDispersed systems consist of two phase: the substance that is dispersed known as the dispersed(or) internal phase and a continuous (or) external phase. Based on the particle size of thedispersed phase, dispersion are generally classifies as molecular dispersion, colloidal dispersionand coarse dispersion.Suspensions are the class of dispersed system in which a finely divided solid is disperseduniformly in a liquid dispersion medium. When one or more type of solid particles thatconstitute the internal phase are pharmaceutically useful and there therapeutically active thesuspensions is known as pharmaceutical suspensions (Herbert A. Lieberman, 1996).

REASONS FOR SUSPENSIONS

There are several reasons for preparing suspensions ((Loyd V. Allen Jr., 2010) & (Alok K.Kulshreshtha, 2009)):

Certain drugs are chemically unstable in solution but stable when suspended. In thisinstance, the suspension ensures chemical stability while permitting liquid therapy.

For many patients, the liquid form is preferred to the solid form of the same drug

because of the ease of swallowing liquids and the flexibility in administration of a rangeof doses. This is particularly advantageous for infants, children, and the elderly.

To overcome the instability of certain drug in aqueous solution:o Insoluble derivative formulated as suspension

An example is ox tetracycline HCL calcium salt(Instable) (Stable)

o Reduce the contact time between solid drug particles and dispersion media increase the stability of drug like Ampicillin by making it as reconstitutedpowder.

o A drug that degraded in the presence of water suspended in non-aqueousvehicles. Examples are phenoxymethypencillin / coconut oil and tetracycline HCL/ oil

The disadvantage of a disagreeable taste of certain drugs in solution form is overcomewhen the drug is administered as undissolved particles of an oral suspension. In fact,chemical forms of certain poor-tasting drugs have been specifically developed for theirinsolubility in a desired vehicle for the sole purpose of preparing a palatable liquiddosage form. For example, erythromycin estolate is a less water-soluble ester form oferythromycin and is used to prepare a palatable liquid dosage form of erythromycin, theresult being Erythromycin Estolate Oral Suspension, USP. Use of insoluble forms of drugsin suspensions greatly reduces the difficult taste-masking problems of developmentalpharmacists, and selection of the flavorants to be used in a given suspension may bebased on taste preference rather than on a particular flavorants ability to mask anunpleasant taste. For the most part, oral suspensions are aqueous preparations with thevehicle flavored and sweetened to suit the anticipated taste preferences of the intendedpatient.


4/13


CLASSIFICATION OF SUSPENSIONS

Suspensions can be classifies based on the characteristics of the dispersed phase or thedispersion medium (Ram I. Mahato, 2007)

Based on the particle size of the dispersed phase:

Coarse Suspensions: Suspensions with the particle size greater than 1m. Colloidal Suspension: Suspensions with the particle size below 1m Nano Suspensions: Suspensions with the particle size 10-100 nm

Based on concentration of the dispersed phase:

Dilute suspension (2 to10%w/v solid) Concentrated suspension ( > 50%w/v solid): Highly concentrated suspensions are termed as

slurries

Based on the routes of administration:

Suspensions as drug dosage forms can be prepared for oral, topical, ophthalmic, otic, and nasalroute of administration. These are briefly described as follows (Leon Lachman, 1986):

Oral Suspensions : Suspensions meant for peroral route of administrations (in which thedrug is swallowed and enters the systemic circulation primarily through the membranesof the small intestine) are usually liquid preparations in which solid particles of theactive drugs are dispersed in asweetened, flavored and usually. Forexample, amoxicillin oral suspensioncontains 125-500 mg/5ml ofsuspension.

Topical suspensions : Lotions areexternally applied suspensions. These

are designed for dermatologic,cosmetic, and protective purposes. For example topical suspension Calamine lotion USP,

contains 118ml of suspension.

Source: http://www.drugs.com/pro/amoxicillin.html

Source : http://newbuy.ca/antiseptic-ointments/95-swan-calamine-topical-suspension-usp-118ml.html
http://www.drugs.com/pro/amoxicillin.htmlhttp://www.drugs.com/pro/amoxicillin.htmlhttp://www.drugs.com/pro/amoxicillin.htmlhttp://newbuy.ca/antiseptic-ointments/95-swan-calamine-topical-suspension-usp-118ml.htmlhttp://newbuy.ca/antiseptic-ointments/95-swan-calamine-topical-suspension-usp-118ml.htmlhttp://newbuy.ca/antiseptic-ointments/95-swan-calamine-topical-suspension-usp-118ml.htmlhttp://newbuy.ca/antiseptic-ointments/95-swan-calamine-topical-suspension-usp-118ml.htmlhttp://www.drugs.com/pro/amoxicillin.html


5/13


Injected Suspensions : Parental suspensions may contain from 0.5% to 30% of solid particles.Viscosity and particle size are significantfactors because they affect the ease ofinjection and the availability of the drug in

the therapy. Most parenteral suspensionsare designed for intramuscular orsubcutaneous administration. For example,procaine penicillin G suspension isintended for the intramuscular

administration.

Rectal suspensions : These are exemplified by the anti-inflammatory 5-acetyl salicylic acid (5-ASA) rectal suspension enema forulcerative colitis.

Source : http://www.drugs.com/pro/mesalamine-rectal-suspension.html

Liposomes and micro-/nano-particles: Suspensions of liposomes, microspheres,microcapsules, nanospheres and nanocapsules are formed from a variety of polymers orproteins. These suspensions formulations are used for targeted and controlled delivery

of drugs.

Several drug delivery systems using liposomes such as Doxil and Daunome are in market.

Source : http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=53683

Source: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15447
http://www.drugs.com/pro/mesalamine-rectal-suspension.htmlhttp://www.drugs.com/pro/mesalamine-rectal-suspension.htmlhttp://www.drugs.com/pro/mesalamine-rectal-suspension.htmlhttp://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=53683http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=53683http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=53683http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15447http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15447http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15447http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=15447http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=53683http://www.drugs.com/pro/mesalamine-rectal-suspension.html


6/13


Otic Suspensions: These ate intended for administration into ear. Most otic suspensionsare antibiotics for the treatment of ear infections and may also be corticosteroids forminimizing inflammation and analgesics for pain relief. and hydrocortisone for antibioticand anti-inflammatory effect

Based on the type of the dispersed system

Aqueous suspensions Nonaqueous suspensions : Although most pharmaceutical suspensions have primarily aqueouscontinuous phase, formulation of a drug in a nonaqueous continuous phase, is occasionallyrequired. Suspensions of a water-soluble drug in a nonaqueous vehicle may provide a means toprepare a liquid formulation of a drug that has poor long-term stability in aqueous solution.Aerosols represent important class of nonaqueous suspensions. The physical stability ofsuspended drugs in non-aqueous propellants for aerosols products can have a significant impacton the uniformity of dose and operation of the aerosol system.

FEAUTRES OF AN IDEAL SUSPENSIONIn contrast to the formulations of the liquid dosage form such as solutions and solid dosageforms such as tablets and capsules, the development and preparation of the suspensionsdosage form involves a great challenge. Pharmaceutical formulations are thermodynamicallyunstable. Formulation of such suspension is difficult because often these systems faces theproblems of physical stability, content uniformity, sedimentation, caking, redispersion andcrystal growth. Moreover, in formulating the pharmaceutical suspension factors such aspalatable for improving the taste and undesirable odor of the drug is also taken intoconsideration.

Following are some desired attributes of a perfect and elegant pharmaceutical suspension (AlokK. Kulshreshtha, 2009)& (Ram I. Mahato, 2007):

1. For a given batch of the suspension the content of drug should remain uniform fromone package to another.

2. For every dose released from the container, the quantity of drug dispensed shouldremain consistent.

3. Physical attributes such as particle size, PSD, viscosity should remain nearly uniformthroughout the shell life of the product.

4. Suspended material should settle slowly and should readily dispersed upon gentleshaking of the container such as it uniformity is maintained with each dose.

5. Particles having lower settling velocity tends to form a hard cake. In an ideal suspension,

these should never happen, but those particles should be readily redispersed upon theshaking.6. Suspension viscosity should be such that, it should pour freely form the bottle or to flow

through a needle syringe (for injectable suspension) or spreads freely on the affectedarea (for topical suspension).

7. There should be no microbial growth.8. The suspension should not show any unexpected change in color or any other change in

physical appearance or odor.9. The suspension should be chemically stable, it should not degrade during the shell life

and storage.


7/13


10. The drug must not recrystallize and/or change its polymorphic form during the storageof the formulation.

These main features of a suspension, which depend on the nature of the dispersed phase, thedispersion medium, sedimentations rate, viscosity and various others factors. And all thefactors that are to be given a due consideration in order to attain the desired features are

described briefly next.

IMPORTANT FACTORS TO BE CONSIDERED IN FORMULATION OF THE SUSPENSIONThere are many considerations in the development and preparation of a pharmaceuticallyelegant suspension. (Loyd V. Allen Jr., 2010). Selection of the API and excipients for theformulation of the suspension should be selected carefully depending on the route ofadministration, end application, and possible adverse effects. The following are the mostimportant factors to be considered during the formulation of pharmaceutical suspensions (AlokK. Kulshreshtha, 2009):

1. Nature of suspended material: Among all the properties of the suspended material, theimportant consideration should be given to the interfacial properties during theformulations of a suspension. Material having low interfacial tension exhibits goodwetting property and readily gets suspended. In contrast, the materials possessing highinterfacial tensions are not easily wetted. For such materials, suspensions is aided byusing surfactants. Surfactants increase wettability of the particles by reducing their

surface tension. The main function of wetting agents: (1) to reduce the contact anglebetween surface of solid particles and wetting liquid via displace the air in the voids (2) -surfactant. Excessive amounts of wetting agents can cause foaming or undesirable tasteor odor.

2. Size of suspended particles: Particle size of any suspension is critical and must bereduced within the range as determined during the preformulation study. Too large ortoo small particles should be avoided. Larger particles will settle faster at the bottom ofthe container and too fine particles will easily form hard cake at the bottom of thecontainer. The particle size can be reduced by using mortar and pastel but in large-scalepreparation different milling and pulverization equipments are used. Limitation inparticle size reduction (after reaching a certain particle size):

Expensive and time consuming Movement of small particles due to Brownian motion cause particles to

aggregate, settle, form hard cake that it is difficult to redispersed

3. Viscosity: For the suspension to be highly viscous, it is necessary that it possess theproperty of shear thinning. The advantage of high viscous dispersion medium is that ithas lower sedimentation rate. The viscosity of the media also affects the velocity ofsedimentation. It decreases as the viscosity of the vehicle increases. The viscosity and


8/13


9/13


Figure: Components and Operation of Aerosol System (Loyd V. Allen Jr., 2010)

Aerosols are used as space sprays, surfacesprays, aerated foams, and for oral inhalation.Aerosols used to provide an airborne mist aretermed space sprays . Room disinfectantsroom deodorizers, and space insecticides

characterize this group of aerosols. Theparticle size of the released product isgenerally quite small, usually below 50 m,and must be carefully controlled so that thedispersed droplets or particles remainairborne for a long time.Aerosols intended to carry the active drug toa surface are called surface sprays or surfacecoating sprays. A great many cosmetic andhousehold aerosol products, including

personal deodorant sprays, hair lacquers andsprays, perfumes and colognes, shavinglathers, toothpaste, surface pesticide sprays, paint sprays, spray starch, waxes, polishes,cleaners, and lubricants (Loyd V. Allen Jr., 2010).

ADVANTAGES OF THE AEROSOL DOSAGE FORM

Some features of pharmaceutical aerosols that may be considered advantages over other typesof dosage forms are as follows (Loyd V. Allen Jr., 2010):

Figure: Pharmaceutical Aerosol ( (Loyd V. Allen Jr., 2010)


10/13


1. Aerosols are easy to use. Medication is dispensed at the push of a button. No ancillaryequipment is needed.

2. Aerosol application is a clean process which requires minimal patient "clean up" after usingthe product.

3. A portion of medication may be easily withdrawn without contaminating the remainingmaterial. If the product is sterile, sterility can be maintained throughout the product's shelflife.

4. The active drug is protected from oxygen and moisture. The usual aerosol container isopaque which also protects the drug from light.

5. By proper formulation and valve control, the physical form and the particle size of theemitted product may be controlled.

6. If the dosage must be regulated, a metered dose valve can be used which will control theaccuracy of the administered dose.

7. Aerosol application is a clean process, requiring little or no washup by the user.

PHARMACEUTICAL AEROSOL APPLICATIONSPharmaceutical aerosols have been playing a crucial role in the health and wellbeing of millionsof people throughout the world for many years. These devices includes:

metered-dose inhalers (MDIs) dry powder inhalers (DPIs)

nebulizersThese devices deliver a specific quantity of drug to the lungs. For the inhalation aerosols, theparticle size distribution and shape of the delivered dose is more critical than for most otherconventional drug products because these factors greatly influence the deposition profile in thelungs of the patient. The optimum aerodynamic particle size distribution for most inhalationaerosols has generally been recognized as being in the range of 1-5 m (Loyd V. Allen Jr., 2010).

METERED DOSE INHALERS (MDI) In the case of the inhalation therapy where the formulation plays a strong role, metering valvesare proven to be a very useful tool. The quantity of the material to be expelled out of thesemetered valve systems, is controlled by an auxiliary valve chamber. The MDI device is made of a

canister, and actuator, and sometimes a spacer.The canister consists of a metering dose valvewith an actuating stem. The canister containsformulation and is made up of the drug, aliquefied gas propellant, and often stabilizingexcipients. Actuation of the device results intoevacuation of this chamber and discharges asingle metered dose of liquid propellant thatcontains the medication. The volatile propellantbreaks up into droplets which then evaporate,

Figure: Working of the Metered Dose Inhaler( http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/ )
http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/http://www.horiba.com/scientific/products/particle-characterization/applications/pharmaceutical-aerosols/


11/13


creating an aerosol containing micronized drug that is inhaled into the lungs. The canister isimpenetrable to the ambient conditions when the actuator valve is close and under thisposition the canister is packed with the formulation. The entire system is reinstated for the nextdose upon the release of the actuator. The quantity of the drug released upon the actuation ismeasured by tests framed by the United States Pharmacopeia. The potential in delivering themedication, its local and systemic effects lies on the particle size of the inhaled drug (Ansel &link). Breathing patterns and the depth of respiration also play important roles in the depositionof inhaled aerosols to the lungs. Analysis of dose uniformity, particle size distribution patternsand the respirable fractions of Aerosol-delivered particles are areas of research in developingaerosol products for optimal oral inhalation therapy (Loyd V. Allen Jr., 2010).

EXAMPLES OF INHALATION AEROSOLS (Loyd V. Allen Jr., 2010):


12/13


PROPER ADMINISTRATION AND USE OF THE PHARMACEUTICAL AEROSOLSAs presented in Table a number of drug substances are administered through pressure-packaged inhalation aerosols like the type shown in Figure. For the inhaled drug substance or

solution to reach the bronchial tree, the inhaledparticles must be just few micron in size. (Loyd V.Allen Jr., 2010)It is the responsibility of the pharmacist to educatethe patient about the aerosol dosage formsimportantly for the oral and nasal administration,effectiveness of these medications lies in theproper usage. Every product package should belabelled and should contain instructions and it isthe duty of the pharmacist to make sure that thepatient read those instructions and warningsbefore they use it. In addition to this, as anassurance that the patients understands the

instructions, the pharmacist should verbally conveythose instructions. For better awareness on theusage of the aerosols, the pharmacist shoulddemonstrate how the inhaler is assembled, stored

and cleaned using the oral metered aerosols as a model. The patient should be instructed aboutshaking prior to use and the manner in which the inhaler should be hold between index fingerand thumb. And this is to make sure that when the patient uses, the aerosol canister is upsidedown. As noted previously, the effectiveness of these dosage forms lies in the proper usage, itis important that the patient understands that there must be synchronization of the inhalationand pressing down the inhaler to release single dose. To achieve the therapeutic effect, the

patient should hold the breath for several seconds or as long as possible and then remove theinhaler from the mouth and exhale slowly (Loyd V. Allen Jr., 2010).

SUMMARYThis report have covered the topic of the suspensions as dosage forms. Suspension dosageforms have become one of the important class of the pharmaceutical dosage form. Thesuspensions dosage form has been traditionally used for poorly soluble drugs for various typesof the dosage formulations. These dosage form is attracting the interests of the scientist aslarge proportions of the new drug candidates that are emerging are mainly water insoluble andtherefore, exhibits poor bioavailability in the solution dosage forms. The advantages of the

suspension dosage include efficient delivery of the hydrophobic drugs; avoidance the using ofcosolvents increasing the stability, masking of the unpleasant taste properties of the drug, easyadministration for the children and elder person (Alok K. Kulshreshtha, 2009). This report hasdiscussed the various types of the pharmaceutical suspensions based on the size of theparticles, based on the concentration & type of the dispersed phase and based on the routes ofthe administration. Pharmaceutical suspensions are major the oral suspensions. Different formsof the pharmaceutical suspensions viz oral, parenteral, rectal etc. are discussed with theirclinical applications. The most important challenge in developing and formulating the pharmaceutical suspension isto preparing an ideal suspension which will maintain the uniform content, remain stable both

Figure: foam for anal and perennial use (Loyd V. Allen Jr.,2010)


13/13


physically and chemically, and maintain the viscosity during the storage and shell life.Therefore, development of the pharmaceutical suspension is very complex process and it isvery important to have better understanding of the properties of the both the dispersed phaseand continuous phase. The most important factors to be considered during the formulationhave been discussed. In the context and limitation of this report only the three main factors

particle size, nature of the media and viscosity have been included. Apart from these factors,there are various other factor such as sedimentation rate, charge stabilization, crystal growth,interactions of the components etc. should be thoroughly understood form the stability of thepharmaceutical suspensions.

The last part of the report deals with the aerosols, one of the most important form of the non-aqueous suspensions. Aerosols is gaining importance in the pharma industry as aerosol therapyis local, rapid and intense. The inhaled drug goes directly into lungs. Different aspects of theaerosols have been briefly described and emphasis is given on the Metered dose inhaler (MDI)as it is the most common pharmaceutical aerosols. The most common challenge that the

scientist is facing is developing more environmentally friendly and safer inhalers. The mostcommon propellant used in the aerosols in the chlorofluorocarbons (CFC) since these haveadverse effect on the ozone layer and also being flammable they threat the patient safety too.So, research is going on in find new and safe propellant.

Further, this report can be extended to the nanosuspensions. Nanosuspensions have emergedas a promising strategy for the efficient delivery of hydrophobic drugs because of their versatilefeatures and unique advantages. Rapid advances have been made in the delivery ofnanosuspensions by oral, ocular, parenteral and pulmonary routes. Currently efforts are beingmade directed to extend their applications in site specific drug delivery (Alok K. Kulshreshtha,2009).

REFERENCES

1. Alok K. Kulshreshtha, O. N. (2009). Pharmaceutical Suspensions: From Formulation Developmentto Manufacturing. New-York: Springer.

2. Herbert A. Lieberman, M. M. (1996). Pharmaceutical Dosage forms: Disperse Systems Volume 1. New-York: Marcel Dekker,Inc.

3. Leon Lachman, H. A. (1986). The Theory and Practice of Industrial Pharmacy . Lea & Febiger.

4. Loyd V. Allen Jr., N. G. (2010). Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems.

Lippincott Williams & Wilkins.5. Ram I. Mahato, A. S. (2007). Pharmaceutical Dosage Forms and Drug Delivery. CRC Press.

Dispersed Systems Consist of Two Phase

Documents

Transcript of Dispersed Systems Consist of Two Phase