A comparative study of the effect of different stabilizers on the critical quality attributes of self-assembling nano co-crystals
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183224 , vital:43931 , xlink:href=" https://doi.org/10.3390/pharmaceutics12020182"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) less than 1000 nm, polydispersity index (PDI) less than 0.500 and Zeta potential (ZP) less than −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.
- Full Text:
- Date Issued: 2020
Assessment of taste masking of captopril by ion-exchange resins using electronic gustatory system
- Authors: Chikukwa, Mellisa T R , Wesoly, Malgorzata , Korzeniowska, Aleksandra B , Ciosek-Skibinska, Patrycja , Walker, Roderick B , Khamanga, Sandile M M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184710 , vital:44265 , xlink:href="https://doi.org/10.1080/10837450.2019.1687520"
- Description: The objective of the study was to mask the unpleasant taste of captopril (CPT). Taste masking was achieved by complexation of CPT with a basic ion exchange resin, Dowex® 66, using the batch method. Dowex® 66 was used for the adsorption of CPT, and physical and chemical parameters of the CPT resinates complex were evaluated. A central composite design was used to generate the experiments for the manufacture of resinates using different process and formulation variables. In vitro dissolution studies were performed for 2 h in 0.01N HCl (pH 1.6) using USP Apparatus I. The compatibility of CPT and the resin was evaluated by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The resinates were evaluated for micromeritic properties and further characterised using FTIR, DSC, and PXRD. Response surface methodology was used to determine the significance of input variables on the CPT content and release. The CPT resin ratio was found to have a significant impact on content of the resinates and on CPT release. The formulations were also studied for taste masking ability by means of an electronic gustatory system – electronic tongue.
- Full Text:
- Date Issued: 2020
Biocompatibility of biomaterials for nanoencapsulation: Current approaches
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Chabalenge, Billy , Mwila, Chiluba , Kalungia, Aubrey C , Nkanga, Christian I , Bapolisi, Alain M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183289 , vital:43939 , xlink:href="https://doi.org/10.3390/nano10091649"
- Description: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
- Full Text:
- Date Issued: 2020
Co-loading of isoniazid-grafted phthalocyanine-in-cyclodextrin and rifampicin in crude soybean lecithin liposomes: Formulation, spectroscopic and biological characterization
- Authors: Nkanga, Christian I , Roth, Michael , Walker, Roderick B , Noundou, Xavier S , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183481 , vital:43999 , xlink:href="https://doi.org/10.1166/jbn.2020.2880"
- Description: An inclusion complex of isoniazid-grafted phthalocyanine with gamma-cyclodextrin (Complex) was co-encapsulated with rifampicin (RIF) in crude soybean lecithin liposomes using a heating method. The encapsulation efficiency (%EE) of the Complex-RIF co-loaded liposomes (Rif-Complex-Lips) was determined using UV-Vis spectrophotometry. Rif-Complex-Lips formulations were evaluated using dynamic light scattering, transmission electron microscopy (TEM), 1H-NMR, absorption and emission spectroscopy. Dialysis was used for drug release study in two different media, pH 6.4 and 7.4. HeLa cells were used to assess potential cytotoxicity, and the uptake by lung fibroblasts and epithelial cells was investigated using fluorescence microscopy. The particle size and Zeta potential of Rif-Complex-Lips were approximately 594 nm and –50 mV. Spectroscopic analyses demonstrated molecular distribution of the cargo within the lipid core, and encapsulation efficiency of 58% for Complex and 86% for RIF. TEM analysis unveiled the existence of spherical nanoparticles in our samples, indicating the presence of liposomes. Rif-Complex-Lips exhibited much higher release rates for both INH and RIF at pH 6.4 compared to those tested at pH 7.4. In addition, there was no cytotoxicity on HeLa cells, but remarkable Rif-Complex-Lips internalization by peripheral lung fibroblasts and epithelial cells. Hence, Rif-Complex-Lips are promising vehicles for intracellular delivery of antimicrobial drugs.
- Full Text:
- Date Issued: 2020
Design, Optimization, Manufacture and Characterization of Efavirenz-Loaded Flaxseed Oil Nanoemulsions
- Authors: Mazonde, Priveledge , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183183 , vital:43919 , xlink:href="https://doi.org/10.3390/pharmaceutics12090797"
- Description: The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
- Full Text:
- Date Issued: 2020
Encapsulation and physicochemical evaluation of efavirenz in liposomes
- Authors: Okafor, Nnamdi Ikemefuna , Nkanga, Christian I , Walker, Roderick B , Noundou, Xavier S , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183414 , vital:43988 , xlink:href="https://doi.org/10.1007/s40005-019-00458-8"
- Description: Antiretroviral therapy remains the most efective means of managing the human immune defciency virus/acquired immune defciency syndrome (HIV/AIDS). Application of therapeutics has been hampered by factors including poor bioavailability of most anti-retroviral compounds (ARV), side efects and an alarming emergence of drug resistant strains of the virus. Recent developments and use of drug delivery systems (DDS) has shown potential for improving the pharmacological profle of ARV. Amongst these complex DDS, liposomes have been explored for delivery of ARV. In this study, we have aimed at exploring efcient encapsulation of efavirenz (EFV), a potent ARV using diferent mass ratios of crude soybean lecithin and cholesterol. The EFV-loaded liposomes (EFL) were prepared using thin flm hydration and evaluated for particle size, zeta potential (ZP), encapsulation efciency (EE%), morphology and drug release studies. Diferential scanning calorimetry (DSC), X-ray difraction (XRD), energy dispersity spectroscopy (EDS) and Fourier transform infrared (FTIR) spectroscopy were used for comprehensive physicochemical characterization of EFL. EFL exhibited high encapsulation (99%) in 1:1 crude lecithin to cholesterol mass ratio. The average particle size and Zeta Potential of EFL were found to be 411.10±7.40 nm and −53.5.3±0.06 mV, respectively. EFL showed a relatively controlled EFV release behaviour that was similar to the dissolution profle of un-encapsulated EFV. This suggests that EFL represents a promising vehicle for efective EFV delivery while providing the advantages of a nano-scaled delivery system
- Full Text:
- Date Issued: 2020
Formulation and Characterisation of a Combination Captopril and Hydrochlorothiazide Microparticulate Dosage Form
- Authors: Chikukwa, Mellisa T R , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183200 , vital:43926 , xlink:href="https://doi.org/10.3390/pharmaceutics12080712"
- Description: Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, prior to administration to paediatric patients. There is a need to develop an age appropriate microparticulate dosing technology that is easy to swallow, dose and alter doses whilst overcoming the pharmacokinetic challenges of short half-life and biphasic pharmacokinetic disposition exhibited by hydrochlorothiazide and captopril. An emulsion solvent evaporation approach using different combinations of polymers was used to manufacture captopril and hydrochlorothiazide microparticles. Design of experiments was used to develop and analyse experimental data, and identifyoptimum formulation and process conditions for the preparation of the microparticles. Characterisation studies to establish encapsulation efficiency, in vitro release, shape, size and morphology of the microparticles were undertaken. The microparticles produced were in the micrometre size range, with an encapsulation efficiency >75% for both hydrochlorothiazide and captopril. The microparticulate technology is able to offer potential resolution to the half-life mediated dosing frequency of captopril as sustained release of the molecule was observed over a 12-h period. The release of hydrochlorothiazide of >80% suggests an improvement in solubility limited dissolution.
- Full Text:
- Date Issued: 2020
Formulation optimization of smart thermosetting lamotrigine loaded hydrogels using response surface methodology, box benhken design and artificial neural networks
- Authors: Melamane, Siyabonga , Walker, Roderick B , Khamanga, Sandile M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183265 , vital:43936 , xlink:href="https://doi.org/10.1080/03639045.2020.1791163"
- Description: The aim of this research was to develop lamotrigine containing thermosetting hydrogel for intranasal administration to manage and treat generalized epilepsy. Thermosetting hydrogels were prepared using different ratios of poloxamer 407 (L127), poloxamer 188 (L68) and CarbopolVR 974 P NF (C974) using the cold production process. The in situ thermosetting hydrogel was optimized using Box Behken design. Co-solvency approach was used to increase the solubility of lamotrigine by dissolving it in propylene glycol and polyethylene glycol 400 (0.2: 0.8) and the resultant solution was incorporated in the hydrogel to manufacture an LTG hydrogel. The presence of a higher amount of L127 resulted in higher viscosity at 22 0C and 34 0C and decreased the overall release of LTG. An increase in the amount of C974 resulted in a decrease in the pH of the hydrogel. The results show that formulations F10, F12, F13, F14, F15, F16 and F17 exhibited acceptable thermosetting behavior, pH and released adequate Lamotrigine above the minimum effective concentration to treat generalized epilepsy. The optimized formulation exhibited acceptable thermosetting behavior, pH and lamotrigine release but formed a stiff gel at 22 0C. The average LTG content of the optimized hydrogel was 5.00 ± 0.0225mg/ml with % recovery of 99.17%. The amount of LTG released at 12 h from the optimized hydrogel was 3.21 ± 0.0155mg and will be therapeutically effective in the brain after absorption via the olfactory region in the nasal cavity.
- Full Text:
- Date Issued: 2020
Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media
- Authors: Mwila, Chiluba , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183210 , vital:43929 , xlink:href="https://doi.org/10.3390/pharmaceutics12030234"
- Description: The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 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 reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
- Full Text:
- Date Issued: 2020
Nano-biomimetic drug delivery vehicles: Potential approaches for COVID-19 treatment
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Mweetwa, Larry L , Ntemi, Pascal V , Chikukwa, Mellisa T R , Matafwali, Scott K , Mwila, Chiluba , Mudenda, Steward , Katandula, Jonathan , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183440 , vital:43991 , xlink:href="https://doi.org/10.3390/molecules25245952"
- Description: The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
- Full Text:
- Date Issued: 2020
Preformulation studies of efavirenz with lipid excipients using thermal and spectroscopic techniques
- Authors: Makoni, Pedzisai A , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183253 , vital:43934 , xlink:href=" https://doi.org/10.1691/ph.2020.0053"
- Description: Investigation and identification of potential lipids for the manufacture of efavirenz loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was undertaken. Polymorphic modification and characteristics of the lipids with the best solubilising potential for efavirenz was explored using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Wide-angle X-ray Scattering (WAXS). Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate (GM) and Transcutol® HP (THP) exhibiting the best solubilising potential for EFV. GM exists in a stable β-polymorphic modification prior to exposure to heat, but exists in an α-polymorphic modification following exposure to heat. However, it was established that the addition of THP to GM revealed the co-existence of the α- and β'-polymorphic modifications of the lipid. EFV (60% w/w) exists in a crystalline state in a 70:30 mixture of GM and THP. Investigation of binary mixtures of EFV/GM and GM/THP, in addition to eutectic mixtures of EFV, GM and THP using FT-IR, DSC and WAXS revealed no potential interactions between EFV and the lipids selected for the production of the nanocarriers.
- Full Text:
- Date Issued: 2020
The impact of formulation variables on the optimization of pilot scale clobetasol 17-propionate creams
- Authors: Fauzee, Ayesha F B , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183275 , vital:43937 , xlink:href="https://doi.org/10.1080/23311916.2020.1804713"
- Description: The impact of formulation variables on the optimization of pilot scale clobetasol 17-propionate (CP) cream formulations was investigated using a Central Composite Design of Experiments. Thirty batches of cream were manufactured and the formulation variables assessed were % v/v propylene glycol, % w/w Gelot® 64, cetostearyl alcohol and glyceryl monostearate content. The responses monitored included viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released at 72 hours. The responses were compared to those of a reference product, Dermovate® cream. ANOVA analysis revealed that viscosity, spreadability, and % CP released at 72 hours were significant formulation responses (p more than 0.05). Cetostearyl alcohol had the greatest impact on quality of pilot scale products. An increase in cetostearyl alcohol resulted in an increase in viscosity, a decrease in spreadability, and a decrease in % CP released at 72 hours. The optimized pilot scale CP formulation contained 46% v/v propylene glycol, 8.6% w/w cetostearyl alcohol, 10.5% w/w glyceryl monostearate, and 3.8% w/w Gelot® 64. The resultant viscosity, spreadability, pH, CP content, extrudability, electrical conductivity, and % CP released were 44633cP, 24.91cm2, 101.23 %, 76.98 g/cm2, 198.23 µS/cm, and 50.23%. The addition of cetostearyl alcohol and Gelot® 64 is critical for establishing a soft formulation that leads to the formation of a mixed crystal bilayer network of high viscosity. The formation of a separate crystalline lipophilic network usually occurs in semi-solid formulations that contain high concentrations of emulsifier, leading to an increase in shear stress and greater physicochemical stability of the formulation. The use of experimental design approaches to formulation development activities, permit evaluation of multiple factors simultaneously, reducing the time and costs associated with product development activities, whilst identifying a composition design space and ensuring stable and effective dosage forms are produced.
- Full Text:
- Date Issued: 2020
The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds
- Authors: Makoni, Pedzisai A , Ranchhod, Janeeta , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183376 , vital:43981 , xlink:href="https://doi.org/10.1016/j.jsps.2020.01.010"
- Description: The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto’s molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT larger than 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.
- Full Text:
- Date Issued: 2020
An artificial neural network approach to predict the effects of formulation and process variables on prednisone release from a multipartite system
- Authors: Manda, Arthur , Walker, Roderick B , Khamanga, Sandile M
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183237 , vital:43933 , xlink:href="https://doi.org/10.3390/pharmaceutics11030109"
- Description: The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone.
- Full Text:
- Date Issued: 2019