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Stability of amorphous azithromycin in a tablet formulation / Prasanna Kumar ObulapuramObulapuram, Prasanna Kumar January 2014 (has links)
It is a well-known fact that drugs can exist in different solid-state forms. These solid-state forms can be either crystalline or amorphous. Furthermore, significant differences are identified between the different solid-state forms of the same drug. Physico-chemical properties that are affected by the solid-state include: melting point, solubility, dissolution rate, stability, compressibility, processability, to name but a few. During the last two decades a significant amount of attention was directed towards the amorphous solid-state forms of drugs. The amorphous form is the direct opposite of the crystalline solid-state. While crystalline forms are constituted by unit cells arranged in a repetitive and structured nature, amorphous forms do not have a long-range order. This lack of order leads to an increase in the Gibbs free energy of such compounds which in turn leads to increased dissolution and solubility. The advantage of improved aqueous solubility and dissolution is a sought after characteristic within the pharmaceutical industry. Improved solubility ultimately could lead to improved bioavailability of a drug. In this study the amorphous nature and stability of amorphous azithromycin was studied. Although previous studies reported that amorphous azithromycin can be easily prepared, there is not a significant amount of data available on the stability of the amorphous form. Furthermore, the effect of milling, mixing, compression, handling and storage on the amorphous form was also investigated.
This study showed that amorphous azithromycin remains stable during milling, mixing and compression. A compatibility study on azithromycin when mixed with tableting excipients showed some incompatibilities and this was helpful information to assist with the choice of excipients to be included in the tablet formulation. During the formulation study it became evident that good formulation strategies can greatly improve the flow properties of a drug.
The stability of amorphous azithromycin was also studied. During this phase of the study an atypical stability indicating method was used in order to determine and demonstrate the stability of amorphous azithromycin. Dissolution studies were used to illustrate the stability of amorphous azithromycin due to the fact that dissolution is the only method that indicates the phenomena of solution-mediated phase transformation of an amorphous form to a stable crystalline form. During the stability study of six months at 40°C ± 75% RH no recrystallisation of the amorphous form to the crystalline form occurred. It was concluded that amorphous azithromycin will remain stable during processing steps, product formulation and manufacturing as well as during storage for a period of six months at elevated temperature and humidity. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015
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Stability of amorphous azithromycin in a tablet formulation / Prasanna Kumar ObulapuramObulapuram, Prasanna Kumar January 2014 (has links)
It is a well-known fact that drugs can exist in different solid-state forms. These solid-state forms can be either crystalline or amorphous. Furthermore, significant differences are identified between the different solid-state forms of the same drug. Physico-chemical properties that are affected by the solid-state include: melting point, solubility, dissolution rate, stability, compressibility, processability, to name but a few. During the last two decades a significant amount of attention was directed towards the amorphous solid-state forms of drugs. The amorphous form is the direct opposite of the crystalline solid-state. While crystalline forms are constituted by unit cells arranged in a repetitive and structured nature, amorphous forms do not have a long-range order. This lack of order leads to an increase in the Gibbs free energy of such compounds which in turn leads to increased dissolution and solubility. The advantage of improved aqueous solubility and dissolution is a sought after characteristic within the pharmaceutical industry. Improved solubility ultimately could lead to improved bioavailability of a drug. In this study the amorphous nature and stability of amorphous azithromycin was studied. Although previous studies reported that amorphous azithromycin can be easily prepared, there is not a significant amount of data available on the stability of the amorphous form. Furthermore, the effect of milling, mixing, compression, handling and storage on the amorphous form was also investigated.
This study showed that amorphous azithromycin remains stable during milling, mixing and compression. A compatibility study on azithromycin when mixed with tableting excipients showed some incompatibilities and this was helpful information to assist with the choice of excipients to be included in the tablet formulation. During the formulation study it became evident that good formulation strategies can greatly improve the flow properties of a drug.
The stability of amorphous azithromycin was also studied. During this phase of the study an atypical stability indicating method was used in order to determine and demonstrate the stability of amorphous azithromycin. Dissolution studies were used to illustrate the stability of amorphous azithromycin due to the fact that dissolution is the only method that indicates the phenomena of solution-mediated phase transformation of an amorphous form to a stable crystalline form. During the stability study of six months at 40°C ± 75% RH no recrystallisation of the amorphous form to the crystalline form occurred. It was concluded that amorphous azithromycin will remain stable during processing steps, product formulation and manufacturing as well as during storage for a period of six months at elevated temperature and humidity. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015
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Formulation and evaluation of amorphous clarithromycin tablets for enhanced dissolutionMongalo, Sello Herlot January 2022 (has links)
Thesis (M. Pharmacy ((Pharmaceutics)) -- University of Limpopo, 2022 / According to the biopharmaceutical classification system, Clarithromycin is
considered a class II molecule with low solubility. Poorly soluble drugs result in low
bioavailability. Various techniques have been studied to improve the solubility of
drugs and subsequently bioavailability. Of these techniques, preparation of
amorphous form is the preferred method because it is a more effortless and
convenient way to improve the aqueous solubility and dissolution of poorly water soluble drugs. The only disadvantage of amorphous materials is that they are less
thermodynamically stable and can recrystallize during processing and storage.
Aim:
The aim of this study is to prepare amorphous form of clarithromycin to improve its
solubility, dissolution rate, and, subsequently, bioavailability.
Methods:
In this study, preparation of amorphous form of clarithromycin was conducted using
the quench cooling method in which the purchased anhydrous crystalline
clarithromycin was spread on an aluminum foil and heated to a melting point (217˚C
- 220˚C) and then rapidly cooled. Various techniques were conducted to
characterize the prepared amorphous clarithromycin, and these include Differential
Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and
X-Ray Powder Diffraction (XRPD). In addition, tablets were formulated using the
amorphous clarithromycin mixed with selected excipients from compatibility studies,
and in vitro dissolution and stability studies were conducted over a period of 6
months.
Results:
The DSC thermogram results confirmed that the material prepared using the
quench cooling process is an amorphous solid-state. Furthermore, the XRPD
confirmed an amorphous solid-state with scattering halo peaks. The FTIR also
depicted some broader and lower intensity peaks that indicated a formation of an
amorphous material. The dissolution rate of amorphous clarithromycin tablets
improved by more than 30% when compared to commercial crystalline
clarithromycin tablets. The study revealed a drop in dissolution rate at months 3 to
6 under accelerated conditions due to recrystallization. The 6 monthly stability study
at long term conditions showed no change in the integrity of the tablets and their
contents.
Conclusion:
As indicated by the study, it can be concluded that the amorphous clarithromycin
remained stable during processing and storage under long-term stability for 6
months. Furthermore, based on dissolution results, it can be concluded that
amorphous solids have an improved dissolution rate. / Medical Research Council
CHIETA
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