Development and assessment of azithromycin paediatric suppository formulations
- Authors: Mollel, Happiness
- Date: 2006
- Subjects: Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3774 , http://hdl.handle.net/10962/d1003252 , Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Description: The use of the oral route of administration for the treatment of young children with antibiotics can at times be problematic since, factors such as nausea, vomiting, taste and/or smell, in addition to the challenges associated with the administration of suspensions, may contribute to poor patient compliance. In such cases, the use of the rectal route of administration may be appropriate. Therefore, suppositories containing 250 mg azithromycin (AZI) were manufactured and assessed for potential as an antibiotic suppository dosage form. Suppositories, containing AZI dihydrate were manufactured by the fusion method, using different grades of PEG, Witepsol® and Suppocire® bases. The rate and extent of AZI release was evaluated using USP apparatus I, and samples were analyzed using a validated HPLC method. Differences in the rate and extent of AZI release were observed with the greatest amount of AZI being released from PEG formulations. The rate and extent of AZI release from formulations manufactured using fatty bases were influenced by physicochemical properties, such as melting rate and hydroxyl value, of the bases. In addition drug partitioning appeared to favor the lipid phase and had a negative impact on AZI release characteristics. Two different formulation approaches were used in an attempt to increase the rate and extent of AZI release from fatty base formulations. The use of surfactants significantly increased AZI release from formulations manufactured with fatty bases with high hydroxyl values. The use of urea or Povidone K25 in combination with AZI as a physical mixture or solid dispersion did not increase the rate and extent of AZI release from the fatty suppositories, to any significant extent. The mechanism of drug release was evaluated using several mathematical models, including the Higuchi, Korsmeyer- eppas, Zero and, First order models. In addition, in vitro dissolution profiles were characterized by the difference and similarity factors, f1 and f2 and by use of the Gohel similarity factor, Sd. AZI release kinetics were best described by the Higuchi and Korsmeyer-Peppas models and the values of the release exponent, n, revealed that drug release was a consequence of the combined effects of AZI diffusion, rate of melting of the base and partitioning of the drug which can be considered to be anomalous release.
- Full Text:
- Date Issued: 2006
- Authors: Mollel, Happiness
- Date: 2006
- Subjects: Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3774 , http://hdl.handle.net/10962/d1003252 , Azithromycin , Pediatrics , Clinical pharmacology , Pharmacokinetics , Suppositories , Drugs -- Dosage forms
- Description: The use of the oral route of administration for the treatment of young children with antibiotics can at times be problematic since, factors such as nausea, vomiting, taste and/or smell, in addition to the challenges associated with the administration of suspensions, may contribute to poor patient compliance. In such cases, the use of the rectal route of administration may be appropriate. Therefore, suppositories containing 250 mg azithromycin (AZI) were manufactured and assessed for potential as an antibiotic suppository dosage form. Suppositories, containing AZI dihydrate were manufactured by the fusion method, using different grades of PEG, Witepsol® and Suppocire® bases. The rate and extent of AZI release was evaluated using USP apparatus I, and samples were analyzed using a validated HPLC method. Differences in the rate and extent of AZI release were observed with the greatest amount of AZI being released from PEG formulations. The rate and extent of AZI release from formulations manufactured using fatty bases were influenced by physicochemical properties, such as melting rate and hydroxyl value, of the bases. In addition drug partitioning appeared to favor the lipid phase and had a negative impact on AZI release characteristics. Two different formulation approaches were used in an attempt to increase the rate and extent of AZI release from fatty base formulations. The use of surfactants significantly increased AZI release from formulations manufactured with fatty bases with high hydroxyl values. The use of urea or Povidone K25 in combination with AZI as a physical mixture or solid dispersion did not increase the rate and extent of AZI release from the fatty suppositories, to any significant extent. The mechanism of drug release was evaluated using several mathematical models, including the Higuchi, Korsmeyer- eppas, Zero and, First order models. In addition, in vitro dissolution profiles were characterized by the difference and similarity factors, f1 and f2 and by use of the Gohel similarity factor, Sd. AZI release kinetics were best described by the Higuchi and Korsmeyer-Peppas models and the values of the release exponent, n, revealed that drug release was a consequence of the combined effects of AZI diffusion, rate of melting of the base and partitioning of the drug which can be considered to be anomalous release.
- Full Text:
- Date Issued: 2006
The geology, petrology and geochemistry of the mineralization and hydrothermal alteration at Ongeama, Ongombo and Matchless West Extension, Namibia
- Authors: Moroni, Marilena
- Date: 1991
- Subjects: Geology -- Namibia , Petrology -- Namibia , Geochemistry -- Namibia
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5045 , http://hdl.handle.net/10962/d1007693 , Geology -- Namibia , Petrology -- Namibia , Geochemistry -- Namibia
- Description: The Matchless Amphibolite Belt (Damara Orogen, Namibia) hosts several volcanogenic-exhalative, sediment-hosted stratiform cupriferous pyrite deposits. These are thought to be related to submarine volcanism during the early evolutionary stages of a narrow Damaran ocean, the Matchless Trough. The mineralized bodies examined (Ongeama, Ongombo and Matchless West Extension) are deformed and metamorphosed to low-medium grade (greenschist-amphibolite facies). They are associated with metapelite and amphibolite country rocks, and crop out as prominent limonite-rich gossans. The elongated shape of the sulphide bodies suggests a structural control. The mineralization normally consists of a variably developed massive sulphide portion, either quartz-, talc- or amphibole-bearing, and a stratigraphically overlying, extensive horizon of sulphide- and baryte-bearing exhalite (magnetite quartzite and less common talc- and actinolite-bearing schists). Lateral and vertical mineralogical changes within the mineralization match with significant variations in the element distribution. A metamorphosed and deformed alteration pipe, indicating the position of the fluid conduit, can be recognized in association with some ore bodies. The formation of quartz-muscovite and chlorite alteration envelopes (Ongeama, Matchless West Extension) and the presence of subtle mineralogical changes (Ongombo) in the immediate wallrocks, accompanied by extensive redistribution, leaching and introduction of elements from outside, suggest the hydrothermal metasomatic origin of the alteration zones. Element zoning within the mineralized bodies can be related to the original position of the vent, possibly coinciding with the intersection of the axis of the alteration pipe with the sulphide body. Cu, Zn, Au (pro parte) and Mo are enriched proximal to the vent, whereas Pb, Ba, Mn, Ag, Au, Sn, Bi and W enrichment characterizes the distal facies of the mineralization. In spite of the obliterating and disrupting effects of the regional dynamo-metamorphism, the element distribution within the mineralization and alteration zones examined is comparable with the geochemical trends observed in present-day mineralizing systems in early- stage oceanic environments (e.g. Guaymas Basin). During exploration for blind volcanogenic mineralization, the detection of hydrothermally altered rocks is fundamental in indicating the proximity to the mineralization. The localization of the alteration zone is also important in the interpretation of the regional geology of the explored area: in deformed terrains the assessment of the stratigraphic position of the alteration zone, relative to the mineralization, helps in establishing the polarity of the sequence.
- Full Text:
- Date Issued: 1991
- Authors: Moroni, Marilena
- Date: 1991
- Subjects: Geology -- Namibia , Petrology -- Namibia , Geochemistry -- Namibia
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5045 , http://hdl.handle.net/10962/d1007693 , Geology -- Namibia , Petrology -- Namibia , Geochemistry -- Namibia
- Description: The Matchless Amphibolite Belt (Damara Orogen, Namibia) hosts several volcanogenic-exhalative, sediment-hosted stratiform cupriferous pyrite deposits. These are thought to be related to submarine volcanism during the early evolutionary stages of a narrow Damaran ocean, the Matchless Trough. The mineralized bodies examined (Ongeama, Ongombo and Matchless West Extension) are deformed and metamorphosed to low-medium grade (greenschist-amphibolite facies). They are associated with metapelite and amphibolite country rocks, and crop out as prominent limonite-rich gossans. The elongated shape of the sulphide bodies suggests a structural control. The mineralization normally consists of a variably developed massive sulphide portion, either quartz-, talc- or amphibole-bearing, and a stratigraphically overlying, extensive horizon of sulphide- and baryte-bearing exhalite (magnetite quartzite and less common talc- and actinolite-bearing schists). Lateral and vertical mineralogical changes within the mineralization match with significant variations in the element distribution. A metamorphosed and deformed alteration pipe, indicating the position of the fluid conduit, can be recognized in association with some ore bodies. The formation of quartz-muscovite and chlorite alteration envelopes (Ongeama, Matchless West Extension) and the presence of subtle mineralogical changes (Ongombo) in the immediate wallrocks, accompanied by extensive redistribution, leaching and introduction of elements from outside, suggest the hydrothermal metasomatic origin of the alteration zones. Element zoning within the mineralized bodies can be related to the original position of the vent, possibly coinciding with the intersection of the axis of the alteration pipe with the sulphide body. Cu, Zn, Au (pro parte) and Mo are enriched proximal to the vent, whereas Pb, Ba, Mn, Ag, Au, Sn, Bi and W enrichment characterizes the distal facies of the mineralization. In spite of the obliterating and disrupting effects of the regional dynamo-metamorphism, the element distribution within the mineralization and alteration zones examined is comparable with the geochemical trends observed in present-day mineralizing systems in early- stage oceanic environments (e.g. Guaymas Basin). During exploration for blind volcanogenic mineralization, the detection of hydrothermally altered rocks is fundamental in indicating the proximity to the mineralization. The localization of the alteration zone is also important in the interpretation of the regional geology of the explored area: in deformed terrains the assessment of the stratigraphic position of the alteration zone, relative to the mineralization, helps in establishing the polarity of the sequence.
- Full Text:
- Date Issued: 1991
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