Development and assessment of minocycline sustained release capsule formulations
- Sachikonye, Tinotenda Chipo Victoria
- Authors: Sachikonye, Tinotenda Chipo Victoria
- Date: 2010
- Subjects: Drugs -- Controlled release , Drugs -- Dosage forms , Capsules (Pharmacy) , Drugs -- Administration , Acne -- Treatment , Tetracyclines , Antibiotics -- Side effects
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3854 , http://hdl.handle.net/10962/d1013127
- Description: The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.
- Full Text:
- Date Issued: 2010
- Authors: Sachikonye, Tinotenda Chipo Victoria
- Date: 2010
- Subjects: Drugs -- Controlled release , Drugs -- Dosage forms , Capsules (Pharmacy) , Drugs -- Administration , Acne -- Treatment , Tetracyclines , Antibiotics -- Side effects
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3854 , http://hdl.handle.net/10962/d1013127
- Description: The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.
- Full Text:
- Date Issued: 2010
A drug utilisation review of Isotretinoin in the management of acne
- Authors: Burger, Solé
- Date: 2007
- Subjects: Acne -- Treatment , Isotretinoin
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:10147 , http://hdl.handle.net/10948/673 , Acne -- Treatment , Isotretinoin
- Description: Acne is a common, chronic disorder that affects many adolescents. The most effective acne medication is systemic isotretinoin. It provides a permanent cure for many patients, but has various side effects. A South African Acne Treatment Guideline was introduced in 2005. Adherence to this guideline could lead to safer, more effective acne management. The primary aim of this study was to investigate the appropriateness of medications prescribed in the treatment of acne in South Africa, and to evaluate the safety and efficacy of systemic isotretinoin utilised by patients in the Nelson Mandela Metropole (NMM). A drug utilisation study (including 18 803 South African acne patients’ chronic prescription data between 2000 and 2005) and a patient questionnaire survey (including information from 57 patients in the NMM who used systemic isotretinoin) were conducted. Basic descriptive and interferential statistics were calculated. The drug utilisation study revealed that systemic antibiotics were the acne treatment prescribed to most (43.3 percent) patients, followed by 42.1 percent of patients on systemic isotretinoin, 33.2 percent on hormonal therapy and 18.9 percent on topical therapy. Topical retinoids were underused. The questionnaire survey indicated a lack of compliance by prescribers with guideline recommendations regarding the prescription (and accompanying counselling and monitoring) of isotretinoin. Incorrect cumulative doses were frequently prescribed, and a lack of proper implementation of pregnancy prevention measures was evident. The majority of isotretinoin patients reported a high efficacy of isotretinoin in clearing their acne.
- Full Text:
- Date Issued: 2007
- Authors: Burger, Solé
- Date: 2007
- Subjects: Acne -- Treatment , Isotretinoin
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:10147 , http://hdl.handle.net/10948/673 , Acne -- Treatment , Isotretinoin
- Description: Acne is a common, chronic disorder that affects many adolescents. The most effective acne medication is systemic isotretinoin. It provides a permanent cure for many patients, but has various side effects. A South African Acne Treatment Guideline was introduced in 2005. Adherence to this guideline could lead to safer, more effective acne management. The primary aim of this study was to investigate the appropriateness of medications prescribed in the treatment of acne in South Africa, and to evaluate the safety and efficacy of systemic isotretinoin utilised by patients in the Nelson Mandela Metropole (NMM). A drug utilisation study (including 18 803 South African acne patients’ chronic prescription data between 2000 and 2005) and a patient questionnaire survey (including information from 57 patients in the NMM who used systemic isotretinoin) were conducted. Basic descriptive and interferential statistics were calculated. The drug utilisation study revealed that systemic antibiotics were the acne treatment prescribed to most (43.3 percent) patients, followed by 42.1 percent of patients on systemic isotretinoin, 33.2 percent on hormonal therapy and 18.9 percent on topical therapy. Topical retinoids were underused. The questionnaire survey indicated a lack of compliance by prescribers with guideline recommendations regarding the prescription (and accompanying counselling and monitoring) of isotretinoin. Incorrect cumulative doses were frequently prescribed, and a lack of proper implementation of pregnancy prevention measures was evident. The majority of isotretinoin patients reported a high efficacy of isotretinoin in clearing their acne.
- Full Text:
- Date Issued: 2007
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