ISSN 2229 – 6832
IJPI’s Journal of Pharmaceutics and Cosmetology
Visit
www.ijpijournals.com
Importance of Bioavailability of Drugs with Reference to
Dosage Form and Formulation
1
Waqar Hussein, 2Shanza Waqar, 3Shumula Khalid, *4Safila Naveed
1
Faculty of Pharmacy Hamdard University
2
CHK, Dow University Health Sciences, Karachi
3
Department of Pharmacology & Therapeutics, D.M.C, DUHS, Karachi
4
Jinnah University for Women Karachi, PAKISTAN
Corresponding author: Safila Naveed Email address:
ABSTRACT:
Drug availability i.e. efficiency of dosage form as drug delivery system is a top issue to pharmacy
and many terms as blood level or significant concentration of drug in the blood stream for distribution
process at the site of action through membrane or amount of metabolite or drug excreted unchanged are used
to describe the phenomena. The absorption depends on the designing of the formation with appropriate
ingredient or excipient, particle size, solubility, dissociation constant pK a, lipid solubility and pH at the
absorption site. The additive e.g. diluents, binder, lubricant, suspending agent, surface active agent often
may alter absorption of a therapeutic agent from a dosage form. Dissolution i.e. release of drug from the
solid dosage form after disintegration is the primary importance for absorption and is rate limiting approved
by FDA. Physicians assume drug administered orally or parenterally reach the general circulation in their
pharmacologically active form to be distributed throughout the body and exert therapeutic effect at the site
of action. It is not true. Complete entry into the general circulation can achieve by intravenous injection.
Keywords: Bioavailability, drug formulations, drug dissolution.
, Vol 2: 7 (2011) IJPI’s Journal of Pharmaceutics and Cosmetology
INTRODUCTION
Drug formulation plays a very vital role for its delivery to the site of action. Variations in formulation of any
drug can affect bioavailability. The Drugs can show different degree of availability from one type of dosage form to
another when given by the same route. The biological availability of a drug is greatly affected by its physical state and
formulation of the dosage form and hence the therapeutic activity of a drug product.
The difference in product formulation can lead to large difference in speed of onset, intensity and duration of
drug response. The study of formulation factors in pharmacological response can be known as the science of biological
availability of particular preparation (Badawy et al., 2006).
Oral route is a preferred rout owing to convenience in application and having a good bioavailability. Solution
form is convenient in both elderly and young patient groups. One of commonly prescribed drugs are cough or cold
medicines, frequently available in solution forms. In oral preparations, solution dosage form is considered to have a
rapid and complete absorption in most of cases. For any oral dosage form, state of stomach and rate of stomach
emptying plays key role in drug absorption. Potent lipophilic drugs having poor water solubility show a poor oral
bioavailability (Kommuru et al., 2001). For these drugs as defined by Amidon et al., 1995 ―low solubility/high
permeability class‖ rate-limiting step in their absorption is dissolution in the lumen. Studies have been conducted to
increase oral bioavailability of lipophilic drugs or otherwise they will not have much clinical efficacy. Such drugs
when prepared in suspension form of finely divided powder show a better bioavailability. Most popular approach used
for these drugs is to incorporate these active lipophilic components into inert lipid vehicles (Aungst, 1993).Such poor
water soluble drugs can be prepared by dissolving them in either water/alcohol or glycerol solvents, oils ( Burcham et
al., 1997) and surfactant dispersions (Serajuddin et al., ;1988 Aungst et al., 1994). Use of self-emulsifying agents has
been suggested in many studies (Wakerly et al., 1986; Charman et al., 1992; Craig et al., 1993; Shah et al., 1994).
Other studies suggest emulsions can be used in this regard (Stella et al., 1978; Palin et al., 1986; Toguchi et al., 1990;
Myers and Stella 1992; Kararli et al., 1992). Liposomes can also be used to dissolve poorly water soluble drugs
(Schwendener and Schott 1996) . All these formulations enhance absorption with advantages and limitations with each
formulation. Compounds with hard crystal structure and non ionic drugs with higher melting points can be prepared
with such types of formulations. It is reported that ―self-emulsifying drug delivery systems‖(SEDDS) are
homogeneous mixtures of natural or synthetic oils, solid or liquid surfactants, or alternatively, one or more hydrophilic
solvents and co-solvents (Constantinides, 1995). The most important quality of these systems is their ability to form
oil-in-water (o/w) emulsions or microemulsions on gentle agitation when followed with aqueous dilution by aqueous
phases. This property causes SEDDS to increase the oral bioavailability of poor water soluble drugs and make them
sufficiently soluble in oils or oil/surfactant formulations (Tatyana and Simon 2000).
A suspension when properly formulated is superior only by a solution in terms of bioavailability. One factor
for absorption is drug dissolution. Suspension containing finely divided powder increases dissolution. There is a strong
relation between the size of particles and rate of absorption. When particles are finely divided, dispersibility increases.
When a surface active agent is added to a suspension, absorption improves. When suspension ages, there is possibility
of increase in particle size. This increase in size can hampers dissolution rate as well as absorption, as small particles
exhibit greater solubility. The smaller the particle size of a drug, the faster the dissolution rate and bioavailability
(Chow and Karara, 1986).
Theoretically drug in capsule dosage form shows a high efficiency. Capsules are thought to achieve better
results as compared to tablets. This is not a rule as in case of poor water soluble drugs. In such cases, use of an oil
based formulation can increase the solubility (Devesh and Pethe, 2010).Lipid agents help in dispersion, minimizing the
aggregation with maximizing the surface area of powdered drug. The state of subdivision of a drug is a primary factor
in pharmacy practice. Particle size can affect the dissolution rate of the drug as it provides more surface area of the
drug or substance in contact with solvent hence greater solubility. The absorption of drug is controlled by how fast the
Safila Naveed Page 39
IJPI’s Journal of Pharmaceutics and Cosmetology
Visit
www.ijpijournals.com
Importance of Bioavailability of Drugs with Reference to
Dosage Form and Formulation
1
Waqar Hussein, 2Shanza Waqar, 3Shumula Khalid, *4Safila Naveed
1
Faculty of Pharmacy Hamdard University
2
CHK, Dow University Health Sciences, Karachi
3
Department of Pharmacology & Therapeutics, D.M.C, DUHS, Karachi
4
Jinnah University for Women Karachi, PAKISTAN
Corresponding author: Safila Naveed Email address:
ABSTRACT:
Drug availability i.e. efficiency of dosage form as drug delivery system is a top issue to pharmacy
and many terms as blood level or significant concentration of drug in the blood stream for distribution
process at the site of action through membrane or amount of metabolite or drug excreted unchanged are used
to describe the phenomena. The absorption depends on the designing of the formation with appropriate
ingredient or excipient, particle size, solubility, dissociation constant pK a, lipid solubility and pH at the
absorption site. The additive e.g. diluents, binder, lubricant, suspending agent, surface active agent often
may alter absorption of a therapeutic agent from a dosage form. Dissolution i.e. release of drug from the
solid dosage form after disintegration is the primary importance for absorption and is rate limiting approved
by FDA. Physicians assume drug administered orally or parenterally reach the general circulation in their
pharmacologically active form to be distributed throughout the body and exert therapeutic effect at the site
of action. It is not true. Complete entry into the general circulation can achieve by intravenous injection.
Keywords: Bioavailability, drug formulations, drug dissolution.
, Vol 2: 7 (2011) IJPI’s Journal of Pharmaceutics and Cosmetology
INTRODUCTION
Drug formulation plays a very vital role for its delivery to the site of action. Variations in formulation of any
drug can affect bioavailability. The Drugs can show different degree of availability from one type of dosage form to
another when given by the same route. The biological availability of a drug is greatly affected by its physical state and
formulation of the dosage form and hence the therapeutic activity of a drug product.
The difference in product formulation can lead to large difference in speed of onset, intensity and duration of
drug response. The study of formulation factors in pharmacological response can be known as the science of biological
availability of particular preparation (Badawy et al., 2006).
Oral route is a preferred rout owing to convenience in application and having a good bioavailability. Solution
form is convenient in both elderly and young patient groups. One of commonly prescribed drugs are cough or cold
medicines, frequently available in solution forms. In oral preparations, solution dosage form is considered to have a
rapid and complete absorption in most of cases. For any oral dosage form, state of stomach and rate of stomach
emptying plays key role in drug absorption. Potent lipophilic drugs having poor water solubility show a poor oral
bioavailability (Kommuru et al., 2001). For these drugs as defined by Amidon et al., 1995 ―low solubility/high
permeability class‖ rate-limiting step in their absorption is dissolution in the lumen. Studies have been conducted to
increase oral bioavailability of lipophilic drugs or otherwise they will not have much clinical efficacy. Such drugs
when prepared in suspension form of finely divided powder show a better bioavailability. Most popular approach used
for these drugs is to incorporate these active lipophilic components into inert lipid vehicles (Aungst, 1993).Such poor
water soluble drugs can be prepared by dissolving them in either water/alcohol or glycerol solvents, oils ( Burcham et
al., 1997) and surfactant dispersions (Serajuddin et al., ;1988 Aungst et al., 1994). Use of self-emulsifying agents has
been suggested in many studies (Wakerly et al., 1986; Charman et al., 1992; Craig et al., 1993; Shah et al., 1994).
Other studies suggest emulsions can be used in this regard (Stella et al., 1978; Palin et al., 1986; Toguchi et al., 1990;
Myers and Stella 1992; Kararli et al., 1992). Liposomes can also be used to dissolve poorly water soluble drugs
(Schwendener and Schott 1996) . All these formulations enhance absorption with advantages and limitations with each
formulation. Compounds with hard crystal structure and non ionic drugs with higher melting points can be prepared
with such types of formulations. It is reported that ―self-emulsifying drug delivery systems‖(SEDDS) are
homogeneous mixtures of natural or synthetic oils, solid or liquid surfactants, or alternatively, one or more hydrophilic
solvents and co-solvents (Constantinides, 1995). The most important quality of these systems is their ability to form
oil-in-water (o/w) emulsions or microemulsions on gentle agitation when followed with aqueous dilution by aqueous
phases. This property causes SEDDS to increase the oral bioavailability of poor water soluble drugs and make them
sufficiently soluble in oils or oil/surfactant formulations (Tatyana and Simon 2000).
A suspension when properly formulated is superior only by a solution in terms of bioavailability. One factor
for absorption is drug dissolution. Suspension containing finely divided powder increases dissolution. There is a strong
relation between the size of particles and rate of absorption. When particles are finely divided, dispersibility increases.
When a surface active agent is added to a suspension, absorption improves. When suspension ages, there is possibility
of increase in particle size. This increase in size can hampers dissolution rate as well as absorption, as small particles
exhibit greater solubility. The smaller the particle size of a drug, the faster the dissolution rate and bioavailability
(Chow and Karara, 1986).
Theoretically drug in capsule dosage form shows a high efficiency. Capsules are thought to achieve better
results as compared to tablets. This is not a rule as in case of poor water soluble drugs. In such cases, use of an oil
based formulation can increase the solubility (Devesh and Pethe, 2010).Lipid agents help in dispersion, minimizing the
aggregation with maximizing the surface area of powdered drug. The state of subdivision of a drug is a primary factor
in pharmacy practice. Particle size can affect the dissolution rate of the drug as it provides more surface area of the
drug or substance in contact with solvent hence greater solubility. The absorption of drug is controlled by how fast the
Safila Naveed Page 39
