https://vital.seals.ac.za/vital/access/manager/Index en-us 5 https://vital.seals.ac.za/vital/access/manager/Repository/vital:4346 Wed 12 May 2021 20:52:33 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:38540 Wed 12 May 2021 16:46:03 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:68596 Tue 07 May 2024 14:52:04 SAST ]]> https://vital.seals.ac.za/vital/access/manager/Repository/vital:28421 85 % isoniazid released at 24 h, implying that the majority of encapsulated isoniazid would be available for absorption. The manufacturing process resulted in the production of hard spherical particles and particle size analysis revealed that the microspheres ranged between 415.76 ± 76.93 μm and 903.35 ± 197.10 μm in diameter. The microspheres exhibited excellent flow properties attributed to the spherical nature of particles. Carr‟s index (CI) was 4.934 ± 0.775 % and the Hausner ratio (HR) was 1.148 ± 0.033 indicating good packability of the microspheres that would help in achieving weight and content uniformity of capsule dosage units. The manufacturing process however produced a low % yield suggesting that scale up difficulties may be encountered. However the high encapsulation efficiency observed may counter the challenges associated with the low yield. The DSC thermograms and FT Raman spectra of 1:1 mixtures of isoniazid, excipients and the microspheres did not reveal any potential detrimental interactions. Microporous floating sustained release microspheres for the delivery of rifampicin in the stomach have been successfully manufactured using emulsification and a diffusion/evaporation process. A novel approach using solvent mixture of acetone and dichloromethane that has not been reported for the manufacture of rifampicin microspheres was successfully used and resulted in the formation of a stable emulsion and the manufacture of rifampicin-loaded microspheres with uniform characteristics. In addition the manufacturing process was shorter than most other reported methods. A Box-Behnken experimental design was successfully used to study the influence of ethylcellulose, Eudragit® RLPO and d-glucose content on the floating properties, encapsulation efficiency and % yield of microspheres. The optimised formulation did not yield desired floating characteristics as the % buoyancy was low and floating lag times were high. The optimised formulation was modified by addition of NaHCO3 to increase the % buoyancy and reduce the floating lag time. Rifampicin release from the microspheres of the modified batch was 87.10 % at 12 h and the microspheres exhibited a % buoyancy of 87.66 ± 1.28 % (n = 6) and floating lag time of 15 ± 3.2 (n = 6) seconds. The microspheres remained buoyant for up to 12 h and an encapsulation efficiency of 88.26 ± 1.25 % was achieved. SEM images of microspheres following exposure to dissolution fluid revealed that the microspheres had numerous pores on their surface. The mean particle size distribution ranged between 423.19 ± 121.86 μm to 620.07 ± 102.67 μm. The microspheres exhibited similar flow characteristics to isoniazid microspheres with a CI of 1.422 ± 0.074 %, and HR of 1.034 ± 0.002. The excellent flow characteristics indicate that filling of the microspheres into hard gelatin capsules was unlikely to pose a challenge in respect of producing a product with uniform content. Rifampicin-excipient compatibility studies did not reveal any potential or significant interactions suggesting that the excipients used for the manufacture of the microspheres were compatible, although long term stability studies would be required to ascertain this is, indeed the case. The microporous floating sustained release microspheres manufactured in these studies has the potential to increase the bioavailability of rifampicin as they may be retained in the stomach where the solubility of rifampicin is high and from which absorption is best achieved. The degradation of rifampicin after 12 h dissolution testing in pH 1.2 0.1 M HCl in the presence of isoniazid gastric-resistant sustained release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be overcome by encapsulation of both active pharmaceutical ingredients in a manner that ensure release in different segments of the gastrointestinal tract. The use of sustained release microporous gastroretentive rifampicin microspheres in combination with sustained release isoniazid gastric-resistant microspheres revealed that accelerated degradation of rifampicin in the presence of isoniazid is reduced significantly when using this approach and a FDC of rifampicin and isoniazid microspheres has the potential to improve the bioavailability of rifampicin thereby enhancing therapeutic outcomes. In vivo studies would be required to confirm the potential benefits of using this approach to deliver rifampicin in combination with isoniazid.]]> Mon 13 Mar 2023 11:57:13 SAST ]]>