physicochemical and bio pharmaceutic considerations

8/2/2019 Physicochemical and Bio Pharmaceutic Considerations

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Physicochemical and

Biopharmaceutic Considerations

Silvia Surini, Ph.D.


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Formulasi Sediaan

1. Studi Praformulasi

2.

Formulasi Bentuk Sediaan3. Kriteria Sediaan

4. Proses Pembuatan

5. Permasalahan

6. Evaluasi Sediaan


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Studi Pra-Formulasi

1. Sifat fisikokimia bahan baku

2. Stabilitas bentuk sediaan3. Faktor kritis dalam proses


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Sifat Fisikokimia

1. Deskripsi fisik

2. Uji mikroskopik

3. Titik leleh

4. Diagram fasa

5. Ukuran partikel

6. Polimorfisme

6. Kelarutan

7. Disolusi

8. Permeabilitasmembran

9. Koefisien partisi

10. Konstanta disosiasi

(pKa)


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Sifat Fisikokimia

1. Deskripsi fisik

Solid kristal / amorf, ukuran partikel,

struktur kristal, titik leleh, kelarutan

Liquid volatile, tdk dpt dibuat tablet (

soft capsule, bentuk garam/ester padatnya)

Gas


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Sifat Fisikokimia

2. Uji mikroskopik

Bentuk partikel / struktur kristal bentuk

sferik/oval mudah mengalir Distribusi ukuran partikel

3. Titik Leleh

Mendefinisikan kemurnian bahan


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Sifat Fisikokimia

4. The Phase Rule Phase diagrams are constructed to provide a

visual picture of the existence of the solid

and liquid phase in binary, ternary and other

mixtures.5. Particle Size

Certain physical and chemical properties of

drug substances are affected by the particlesize distribution: drug dissolution rate,

bioavailability, content uniformity, taste,

texture, color, stability, flow characteristics,

sedimentation rates.


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Sifat Fisikokimia

6. Polymorphism Exhibit different physical-chemical

properties (melting point & solubility).

Amorphous form is more soluble

7. Solubility

A drug must possess some aqueous solubility

for therapeutic efficacy.

The chemical modification of the drug intosalt or ester forms is a technique frequently

used to obtain more soluble compound.


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Sifat Fisikokimia

8. Dissolution Dissolution rate (the time that takes for the

drug to dissolve in the fluids at the

absorption site) is the rate-limiting step in

the absorption process.9. Membrane Permeability

To produce a biological response. The drug

molecule must first cross a biological membrane

Assessing the absorption efficiency,pharmacokinetic parameters and to establish

possible in vitro/in vivo correlation fordissolution and bioavailability.


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Sifat Fisikokimia

9. Partition Coefficient

The octanol-water partition coefficient iscommonly used.

10. pKa/Dissociation Constants

The extent of dissociation/ionization is, in many cases,highly dependent on the pH of the medium containingdrug.

In formulation, often the vehicle is adjusted to a certain

pH in order to obtain a certain level of ionization of thedrug for solubility and stability purposes.

in water)drugof(Conc.

octanol)indrugof(Conc.P

P is dependent on the drug concentration only if the drugmolecules have a tendency to associate in solution.


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Biopharmaceutic Considerations

The concentration of the drug that achieved atthe site of its action depends on the dosage ofthe drug administered, the extent of itsabsorption and distribution to the site, and the

rate and extent of its elimination from thebody.

The area of study embracing this relationship

between the physical, chemical and biologicalsciences as they apply to drugs, dosage form,and to drug action, has been given thedescriptive term biopharmaceutics.


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Drug Absorption

Before an administered drug can arrive at its site ofaction in effective concentration, it must surmount anumber of barriers biologic membranes.

A drug substance must pass more than one of themembrane types before it reaches its site action.

For instance, a drug taken orally.

Drug penetration to the biologic membranes

1. By passive diffusion

2. Through specialized transport mechanisms


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Dissolution and Drug Absorption

Surface Area

Crystal or Amorphous Drug Form

Salt Form

Other Factors (state of hydration,

complexation phenomenon)


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physicochemical and bio pharmaceutic considerations

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