Factors Affecting Drug Absorption (Pharmaceutical factor) SALMAN BIN ABDUL AZIZ UNIVERSITY COLLEGE OF PHARMACY Factors Affecting Drug Absorption (Pharmaceutical factor) PHARMACEUTICS- IV (PHT 414 ) Dr. Mohammad Khalid Anwer 4/22/2017 L8

Pharmaceutical Factors Nature and type of dosage forms:- Solutions Suspensions Tablets Capsules Coated tab Enteric coated tab Excipients and adjuvant Product age and storage conditions. Disintegration test Dissolution test 4/22/2017 L8

MEANS Absorption rate depends on the dosage NATURE AND TYPE OF DOSAGE FORM MEANS Absorption rate depends on the dosage Form which is administered, ingredients used, procedures Used in formulation of dosage forms. The availability of the drug for absorption from the dosage forms is in order. Solutions > Suspensions > capsules > Compressed Tablets > Coated tablets. 4/22/2017 L8

SOLUTIONS Shows maximum bioavailability and factors affecting Absorption from solution are as follows Chemical stability of drug Complexation: between drug and exipients of formulation to increase the solubility, stability. 3. Solubilization: incorporation of drug into micelles to increase the solubility of drugs. 4. Viscosity 5. Type of solution: Whether aqueous or oily solution. 4/22/2017 L8

It comes next after solutions with respect to bioavailability SUSPENSIONS: It comes next after solutions with respect to bioavailability Factors that affects absorption from suspensions are Particle size and effective surface area of dispersed phase 2. Crystal form of drug: some drug can change their crystal structure. Eg. Sulfathiazole can change its polymorphic form, it can be overcome by addition by adding PVP. 3. Complexation: Formation of nonabsorbable complex between drug and other ingredients. Eg. Promazine forms a complex with attapulgite. 4/22/2017 L8

4. Inclusion of surfactant Eg. The absorption of phenacitin from suspension is increased in presence of tween 80. 5. Viscosity of suspension Eg. Methyl cellulose reduces the rate and absorption of nitrofurantoin 6. Inclusion of colourants: Eg. Brilliant blue in phenobarbitone suspension. 4/22/2017 L8

CAPSULES Two types of capsule Hard gelatin capsule 2. Soft gelatin capsule 4/22/2017 L8

Capsules For hard gelatin capsules the shell should disrupt quickly and expose the contents to the GI fluids. Factors influencing are particle size, density, crystal form of the drug, selection of diluents. For hydrophobic drugs with a fine particle size in capsule results in decrease in porosity of the powdered drug and thus decreased penetrability by the solvent which results clumping of particle. soft elastic capsule dissolve faster than hard gelatin capsule & tablets. Which shows better bioavailability from oily solutions, emulsions, or suspensions. The problem with SGC is high water content of shell, moisture migrate in to the shell causes crystallization of the drug results in altered dissolution characteristics . 4/22/2017 L8

The rate of absorption of drugs from capsule is function HARD GELATIN CAPSULE The rate of absorption of drugs from capsule is function Of some factors. 1.Dissolution rate of gelatin shell. 2.The rate of penetration of GI fluids into encapsulated mass 3.The rate at which the mass disaggregates in the GI fluid 4. The rate of dissolution. 5. Effect of excipients; a).Diluents b).Lubricants c). Wetting characteristics of drug d).Packing density 4/22/2017 L8

SGS may used to contain non aqueous solution or liquid or semi solid. SOFT GELATIN CAPSULE SGS has a gelatin shell thicker than HGS, but shell is plasticized by adding glycerin, sorbitol. SGS may used to contain non aqueous solution or liquid or semi solid. SGC have a better bioavailability than powder filled HGC and are equivalent to emulsions. Eg. Quinine derivative was better absorbed from SGC containing drug base compared with HGC containing HCl salts. Grieseoflavin exhibited 88% absorption from Soft Gelatin Capsules compared to HGC(30%) 4/22/2017 L8

TABLETS 1.Compressed tablets 2. Coated tablets 4/22/2017 L8

Compressed Tablets This is the most widely used dosage form. Problem with this arises from reduction in the effective surface area due to granulation & subsequent compression in to dosage form. Tab disintegration and granule disaggregation are the imp steps in absorption process. Compression force also may be an important factor. Disintegration is the rate limiting step for this. 4/22/2017 L8

Bioavailability are more due to large reduction in surface area. Compressed tablets Bioavailability are more due to large reduction in surface area. A B Intact tablets a granules primary drug particles K2 K1 K3 Drug in GI fluid K4 Drug absorbed in body 4/22/2017 L8

The rate constants decrease in the following order. K3>>K2>>K1 The overall dissolution rate and bioavailability of a poor Soluble drugs is influenced by 1.The physicochemical properties of liberated particles. 2. The nature and quantity of additives. 3. The compaction pressure and speed of compression. 4. The storage and age of tablet 4/22/2017 L8

Na Salicylates + starch = Faster dissolution 1.Effect of diluents : Na Salicylates + starch = Faster dissolution Na salicylates + lactose=Poor dissolution. 2.Effect of Granulating agent: Phenobarbital + Gelatin solution=Faster dissolution Phenobarbital+PEG 6000= poor dissolution. 3.Effect of lubricants: Magnesium stearate will retard the dissolution of aspirin tablet Whereas SLS enhance the dissolution. 4/22/2017 L8

4.Effect of disintegrants: Starch tend to swell with wetting and break apart the dosage form. It is reported that 325mg of salicylic acid tablet were prepared by using different concentrations (5%,10%,20%) and max. dissolution was achieved With 20% starch. 5. Effect of colorants: 6.Effect of Compression force: 4/22/2017 L8

Coated tablets Coat is generally used to mask unpleasant taste & odor & to protect the ingredients from decomposition during storage. This adds an additional barrier between GIT & drug. It should get dissolve before tablet disintegration & dissolution. 4/22/2017 L8

COATED TABLETS Cont……………..: There are three types of coating Sugar coating Film coating Enteric coating Sugar coating will take more time than film coating. Care should be taken while selecting the coating material Ex: methyl cellulose which retards the dissolution SUGAR COATING: Sugar,Shellac,fatty glycerides, bees wax, silicone resin Sub coating agent: Talc,acacia,starch. FILM COATING: Polymers, dispersible cellulose derivatives like HPMC CMC. 4/22/2017 L8

Enteric coated tablets It is a special film coated design to restricts the gastric fluids & to dissolve in small intestine. Protect the drug from the degradation in the stomach Ex: erythromycin. Minimize the gastric distress caused by some drugs. Ex: aspirin. These tablets must empty the stomach before the drug absorption can begin. The polymers with pKa values ranging from 4-7 have been found to use. Shellac, cellulose acetate phthalate etc. 4/22/2017 L8