2. INTRODUCTION
• The co-crystallization is a novel technology for pharmaceutical formulations to meet the new therapeutic needs.
The water insoluble drugs taken orally have the problems of less solubility and dissolution rate which results in
poor bio-availability
• The pharmaceutical properties of a drug can be improved by making the co-crystals due to this reason
nowadays the industry taking great interest in the formulation of co-crystals. As there is no need of changing
the structure of API’s( active pharmaceutical ingredients) in co-crystals, the time for the development of drugs
can be reduced by forming the co-crystals.
• Rifampicin (rif) is one of the anti-tubercular first line drug with fixed dose combination (fdc) therapy for
the treatment of tuberculosis. Regarding its treatment, in combination with standard therapeutic protocol
(including pyrazinamide, rifampicin and isoniazid,) and considered to be the most effective one
3. PHARMACEUTICAL CO-CRYSTAL
Pharmaceutical co-crystals are defined as
crystals consisting of two or more neutral
molecules in stoichiometric proportions and bonded toge
ther by non-covalent interactions (for example, hydrogen
bonding and van der Waals force).
4. LITERATURE REVIEW:
• The pharmaceuticals co-crystals have created the field of transformation of the solid-state of drugs, which
have potential application in the enhancement of solubility. It has improved the physicochemical properties of
the drug molecule without altering the pharmacological activities.
• The research organizations have established regulatory standards to describe the status of co-crystals. Almost
70% of the novel drugs introduced by the pharmaceutical companies do not have good water solubility and
dissolution rate which eventually decreased the bio-availability. Low bio-availability of RIF is the cause for the
poor therapeutic outcomes includes drug resistance and failure of therapy. Co-crystallization technique is
successful for the treatment of HIV related drugs, tuberculosis and antibacterial drugs.
• It is expected from the formulation scientist to improve significantly the properties of pharmaceutical co-
crystals and their formulations,. In-vitro and ex-vivo studies have been carried out for the evaluation of the
RIF co-crystals. Dissolution is defined as: "the amount of material that release in a unit time under standard
conditions of liquid-solid interface, solvent composition and temperature". Humidity, light, and temperature
are some of the factors that influence the pharmaceutical product stability. There is a lot of research study
based on low-bio-availability and chemical instability of rifampicin, however no research work has been
reported on RIF co-crystals in the literature.
5. MATERIALS AND METHODS
• In vitro drug release studies A dissolution test will be performed for the co-crystal samples in different
media, i.E., Intestinal conditions , gastric condition and using usp-type 2 dissolution tester.
• In-vitro antibacterial activity the "resazurin assay" will be performed for in-vitro anti-bacterial effect of
co-crystals. Co-crystals dispersed in suitable buffer will be added. The plates will be incubated in a
humidified incubator at 37 C for 5 days. Resazurin dye solution and tween-80 will be added in each well,
and further incubated for 48 hours.
• After the incubation, a mixture of resazurin solution and tween-80 will be added to each well. The lung
parts will be rubbed through a metal screen of a sieve with pores. The availability of the rifampicin co-
crystal will be performed to assess the systemic availability of new formulation and compare with the
existing formulation.
6. CONTINUES……
• The animals will be administered the new rifampicin co-crystal and the concentration of the drugs
will be studied using different time point as reported previously.
• Assessment of safety profile the toxicity profile of the new co-crystallized rifampicin dosage form
will be investigated using previously reported method.
7. PLAN OF WORK:
Work of plan 1st quarter 2nd
quarter
3rd
quarter
4th quarter
1 2 3 4 5 6 7 8 9 10 1
1
12
Literature
survey
Experimenta
l work
Data
analysis &
Thesis
writing
Time duration
8. AIMS AND OBJECTIVES
• The aim of this study is to evaluate the already developed co-crystalline dosage
form of rifampicin in order to enhance the solubility and ultimately the bio-
availability.
• The objectives of the study are:
1. To assess the in vitro release profile of the rifampicin co-crystals
2. To assess bio-availability profile of the rifampicin co-crystal
3. To investigate the in vitro toxicity of the rifampicin on the cell viability of the primary
macrophages
4. To assess the in vivo toxico-kinetic profile of the new rifampicin.
9. SOCIO-ECONOMIC IMPACT
The TB is one of the leading cause of morbidity and mortality in Pakistan, while its reported cases are
increasing annually. The TB have great effect on the social life of the peoples and great care should be
employed to avoid the spread of the TB in close contact peoples. Similarly, the TB not influence the
social life of the peoples but also significantly effect the economy of the country like Pakistan in
different ways.
The health care setups in Pakistan is already under stress and emergence of the resistant cases of
MDR-TB has also put a great burden on the hospitals. Because the resistant cases of TB are associated
with multiple complication including COPD and respiratory collapse due to continues inflammatory
and fibrotic process. Thus, formulating of co-crystallized rifampicin dosage form will not only improve
the bio-availability of the drug but also improve the compliance, therapeutic outcome, reduce the
emergence of resistance and stress on the health care setups.
