Rectal drug delivery system [RDDS]

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A seminar on

1Rectal Drug Delivery System [RDDS]Mr. Sagar Kishor Savale[Department of Pharmaceutics][email protected] of Pharmacy (Pharmaceutics) | Sagar Savale6/19/2016Sagar Kishor Savale

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CONTENT:2IntroductionAnatomy & physiology of rectumAbsorption from rectumFactor influencing drug absorptionMonitoring drug absorption SuppositoryEnemasRectal capsuleAdvantagesDisadvantagesApplicationsConclusionReferences

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INTRODUCTION:3History: In the 18th century, a French pharmacist, Baume used rectal route for administration of suppositories.

Definition: Rectal drug delivery system means administration of drug or pharmaceutical preparations via rectum for local or systemic effect. example: suppositories, rectum tablets and capsules, semisolids enemas, etc.

Rectal products may be:Solid unit dosage form: Suppository.Liquid unit dosage form: Enema. Semi-solid dosage form: Ointment, Cream.6/19/2016Sagar Kishor Savale

ANATOMY AND PHYSIOLOGY OF RECTUM :4

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ANATOMY AND PHYSIOLOGY OF RECTUM :5

The rectum is about 15 to 20 cm long and 1.5 to 2 cm in width.

It hooks up with the sigmoid colon and with the anal canal.

It is a hollow organ with a relatively flat wall surface, without villi and with only three major folds, the rectal valves.

The rectal wall is formed by an epithelium which one cell layer thick.6/19/2016Sagar Kishor Savale

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The rectal tissues are drained by the inferior, middle and superior haemorrhoidal veins, but only the superior vein connects with the hepatic-portal system.

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Under normal conditions, the rectum emptying and filling provokes a defecation reflex which under voluntary control.

The transverse folds in rectum keep stool in place until the person is ready to go to the toilet.

Rectum contains about 2 to 3 ml of mucous, which has a pH of 7.4.

The entire surface area of rectum is 200 - 400 cm2.6/19/2016Sagar Kishor Savale7

ABSORPTION FROM RECTUM:8Medicaments absorbed in the lower part of the rectum are delivered directly into the systemic circulation, thus avoiding any first-pass metabolism.

Thus keeping the drug in the lower part of the rectum would be advisable.

The drug in unionize with high partition coefficient is readily absorbed.

However, it has been found that suppositories can settle high enough in the rectum to allow drug absorption.

The process of absorption will be passive diffusion.

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Factors Influencing Drug Absorption:9Physiological factors:

1. Quantity of dissolution fluid available:

Very small volume under normal conditions.

Under non-physiological conditions the volume is enlarged.

Thus, absorption of slightly soluble drugs will be dissolution rate limited. (e.g. phenytoin)

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2. Properties of rectal fluidsComposition, viscosity and pH of rectal fluids have great effects on drug bioavailability.

3. Contents of the rectum Faecal content

4. MotilityUpright position Wave of contraction from colon6/19/2016Sagar Kishor Savale

11B. Physiochemical factors: 1. Solubility: Higher the solubility, consequently higher the dissolution rate and better is absorption.2. Degree of ionization: At the alkaline pH of rectal mucosa, basic drugs will exist in their unionized form and readily absorbed. 3. Particle size: The smaller the size, the more readily the dissolution of the particle and the greater the chance for rapid absorption.

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124. pH: Rectal content is slightly alkaline (pH 7-8) , so alkaline drugs are quickly absorbed than acidic drugs.

5. Partition Coefficient: Higher the partition coefficient of drug, more readily absorption of drug.6/19/2016Sagar Kishor Savale

MONITERING DRUG ABSORPTION:13Enhancing agent:- e.g. salicylates bile salts fatty acid pH controlSolubilizing agents

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SUPPOSITORY:14Suppository is solid unit dosage form used for rectal administration and which is composed of active drug molecule with water soluble or fatty bases.The suppository melt at body temperature and weight is vary in 1 g (children) to 2.5 g (adults). TYPE OF BASES:BASESM.P.SOLIDIFICATION POINTFatty Bases1) Cocoa butter30-35242) Hard butter36-4532-40Water Soluble BasesPEG38-4938-422) Tween 6135-49-

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Methods of manufacturing of suppository:15Hand molding:The base and other ingredients are triturated well then rolled into a uniform cylinder with a large spatula and cut that cylindrical suppository mass into required size piece. Compression molding:In the compression machine, the suppository mass is placed into a cylinder which is then closed. Pressure is applied from one end to release the mass from the other end into the suppository mold or die. The additional pressure is applied to mass in the die, the formed suppository ejected. Pour molding:

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Enemas and MicroenemasEvacuant Enema: Volume may be up to 2 liters. e.g.- soft soap enemas

Retention Enemas: Volume does not exceed 100 mL. e.g.- Prednisolon enemas

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Rectal Capsule:

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ADVANTAGES:

Infants and children, who have difficulty in swallowing oral medicine. Avoidance of first pass metabolism when given orally. example- Lidocaine, Morphine.

In cases of nausea and vomiting act as alternative route of administration.

Its contact with digestive fluid is avoided. example- Penicillin, vitamins. 6/19/2016Sagar Kishor Savale18

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Drugs which causes gastric irritation or ulceration are administered in rectum. example- Aceclofenac.

Drug absorption may be easily discontinued in an events of accidental overdose.

Drug absorption is not influenced by ingestion of food and the rate of gastric empting.6/19/2016Sagar Kishor Savale

DISADVANTAGES:20 Surface area of rectum is far small for absorption.

Fluid content of rectum is much smaller.

Microbial degradation may occur in rectum.

Patient acceptability may be a problem.

Development of proctitis.(inflammation of rectum)

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APPLICATIONS:Local effect:In case of pain, itching and hemorrhoidsLocally active drugs include astringents, antiseptics, local anesthetics, vasoconstrictors, anti-inflammatory drugs, soothing and protective agents and some laxatives

Systemic effect:Anti-asthmatics, anti-rheumatics and analgesics.

Drugs administered by this route include aspirin, paracetamol, theophylline and few barbiturates, etc.6/19/2016Sagar Kishor Savale21

REFERENCES:22Lakshmi Prasanna J., Deepthi B. and Rama Rao N., Rectal drug delivery: A promising route for enhancing drug absorption, Asian Journal of Research in Pharmaceutical Science, 2012, Vol-2, page no.:143-149.

Pushkar Baviskar, Anjali Bedse, Sayyed Sadique, Vikas Kunde and Shivkumar Jaiswal, Drug Delivery on Rectal Absorption: suppositories, International Journal of Pharmaceutical Science, 2013,(21)1, page no.: 70-76.

D. M. Brahmankar and S. B. Jaiswal, Biopharmaceutics and Pharmacokinetics a treatise, second edition, 2009, Vallabh prakashan, page no.- 83.

Ross and Wilson , Anatomy and Physiology in Health and illness, Churchill Livingstone, 11th edition, page no.: 277-290.6/19/2016Sagar Kishor Savale

James Swarbrick and James C. Boylan, Encyclopedia of Pharmaceutical Technology, second edition, volume 1, A-D, pages 1-1032, page no.932-943.

www.encyclopedia.com/rectal drug delivery (01/03/2016, 01:30pm)

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