Novel Biomimetic Polymeric Nanoconjugates as Drug Delivery Carriers for Poorly Soluble Drugs

Active Pharmaceutical Ingredients with poor solubility have presented significant difficulties in drug product design and development including slow and ineffective absorption leading to inadequate and variable bioavailability. Therefore it has become increasingly desirable to overcome the low aqueous solubility of drug candidates and develop more novel and innovative formulation approaches to increase the dissolution rate of the poorly soluble drugs. This work focuses on the formulation of novel amorphous ibuprofen-polymer nanoconjugates based on the polymer-drug complexation in order to improve its physical and dissolution characteristics without the use of toxic organic solvents. Plain and ibuprofen-loaded binary and ternary nanoconjugates were prepared using four modified co-precipitation techniques including melt solubilization; alkaline solubilization; surfactant solubilization and hydrotropic complexation techniques. A remarkably high loading capacity was achieved ranging from 89.05 to 99.49% across the four techniques and polymer-polymer ratio of 50:50 was found to be most efficient. All the four techniques reduced the size of ibuprofen (2.87 µm) significantly in the presence of 2.0 x10-3 mM of Diethylaminoethyl Dextran (DEAE-Dextran) in the order melt solubilization (203.25 nm) > alkaline solubilization (185.68 nm) > surfactant (Tween 80) solubilization (122.17 nm) > hydrotropic complexation (77.92 nm). 5.0 x 10-4 mM of chitosan also reduced the size of ibuprofen from 2872.12 to 10.70 nm (268-fold reduction). The FTIR spectroscopic analysis revealed electrostatic, hydrophobic and hydrogen bonding interaction between solubilized ibuprofen and the cationic polymers (DEAE-Dextran and chitosan) to form a new product (an amide). Polymer-polymer complexation also occurred between DEAE-Dextran and gellan as well as chitosan and gellan to a different extent depending on the mixing ratios. 1H and 13C NMR analysis confirmed the conjugation between ibuprofen and each of the cationic polymers as well as the formation of a new amide product. DSC thermal analysis showed that the nanoconjugates exhibited new broad and diffuse peaks confirming that they did exist in amorphous state as multiple complexes. The TGA thermograms of the binary nanoconjugates exhibited one step degradation profile compared with the physical mixture which exhibited two steps. However the ternary nanoconjugates exhibited two steps degradation profile confirming the formation of multiple complexes. Marked enhancement of drug release was achieved by the four techniques compared with the ibuprofen control. All the DG (DEAE-Dextran - Gellan) complexes exhibited a higher release profile than ibuprofen control. Fickian and non-Fickian anomalous mechanisms were deduced for the drug release of ibuprofen from the binary conjugates. The ternary nanoconjugates exhibited non-Fickian (anomalous) diffusion, Fickian diffusion and Super Case II transport release mechanisms. The ternary nanoconjugate hydrogels exhibited complete release (100%) within 48 h. The lowest concentration of DEAE-Dextran, Gellan – Ibuprofen – DEAE-Dextran (GIbDD) 2:0.125, increased the release of ibuprofen by 13.4% however higher concentrations of DEAE-Dextran decreased the release profile steadily. It was concluded that DEAE-Dextran has potentials in the formulation of modified (extended) release of ibuprofen. The most prominent mechanism of release of ibuprofen from the nanoconjugate hydrogel was Super Case II transport. SEM and AFM micrographs of the drug loaded composite pharmaceutical films exhibited concentric spheres with two and three layers for the binary and ternary films respectively. This supports the evidence of internalization of ibuprofen by the polyelectrolyte complex. The FTIR and DSC results confirmed electrostatic and hydrophobic interactions between ibuprofen and DEAE-Dextran as well as between gellan and DEAE-Dextran. Thermal analysis revealed that plain bilayer films were thermally more stable than composite films. The addition of ibuprofen significantly increased (p < 0.05, n = 4) the swelling ratio of the films compared with films without the drug. The drug loaded bilayer films exhibited Fickian diffusion mechanism while the dominating mechanism for composite films was anomalous (Non-Fickian) transport. From the foregoing, it was evident that ibuprofen-polymer nanoconjugate present a novel tool for the delivery of ibuprofen with potential application for transdermal delivery

Evaluation of Terminalia macroptera (Combretaceae) Guill. & Perr stem bark extract incorporated into an emulgel for the potential management of rheumatoid arthritis

Background: Rheumatoid Arthritis (RA) is a chronic disease which causes inflammation and damage to the joint. The goals of treatment are to stop inflammation, relieve symptoms, improve physical function and overall well-being. The purpose of this study was to evaluate Terminalia macroptera stem bark (TMB) ethanol extract and formulate it into an herbal emulgel (TME) for the potential management of RA. Methods: Phytochemical analysis and anti-inflammatory activity of TMB were first evaluated using standard analytical methods and complete Freund’s adjuvant (CFA) induced arthritis model in rats respectively. Post-formulation, physical characterization of the carbopol 940 based herbal emulgels (TME) and the reduction in the induced rat paw sizes by the herbal emulgels were evaluated using diclofenac emulgel as the positive control. Results: Phytochemical screening revealed the presence of flavonoids, tannins, terpenoids, saponins, and alkaloids. Inflammatory activity of the extract gave the highest percentage inhibition with TMB (50 mg/kg). The formulated herbal emulgels had good spreadability, extrudability, pH ranging from 4.5±0.2 to 6.9±0.4 and viscosity ranging from 0.36 ± 0.20 to 8.37 ± 0.65 Pas at 6 rpm and 0.26 ± 0.01 to 10.67±0.96 Pas at 12 rpm. TME emulgel significantly (p < 0.05) reduced oedema formation and arthritic index induced by complete Freund’s adjuvant in rats. TME showed dose-dependent anti-inflammatory activity comparable with commercial diclofenac emulgel. Conclusion: TMB showed an excellent inhibitory activity on the induced paw of the tes

Efficacy of topical acne agents in the treatment of Acne Vulgaris: Insights from a meta-analysis

Topical therapies are essential for controlling Acne Vulgaris because they have specific therapeutic effects on the skin. Through a meta-analysis, this study seeks to determine the effectiveness of topical acne treatments in the management of Acne Vulgaris. Data extraction and systematic study of literatures were both included in the methodology utilized for this meta-analysis. Controlled clinical trials and randomized controlled trials comparing topical acne treatments with placebos were included as inclusion criteria. The search strategy used techniques for assessing the quality of results, additional sources, and electronic databases. The pooled effect sizes and publication bias were computed using a random effects model. The results were presented as effect estimates, confidence ranges, and significance levels. The RR estimate for the common effect model is 5.1986, and the 95% confidence interval is [3.8070; 7.0990]. According to this, persons who receive topical acne treatments have a 5.1986 times higher chance of getting a good result than those who receive a placebo. Overall, there isn't much proof of publication bias in the meta-analysis of topical pharmaceutical therapies for Acne Vulgaris, according to the findings of the linear regression test of funnel plot asymmetry. These results provide useful insights into the use of topical treatments for Acne Vulgaris and highlight the targeted mechanism of action, rigorous clinical study designs, consideration of heterogeneity, and statistical significance of the topical acne agents

Characterization of Ceiba petandra and Lannea kerstingii Stem Bark Extract Creams

A study on physicochemical characteristics of Ceiba petandra and Lannea kerstingii stem bark extracts cream being developed for the treatment of topical dermatophytic infections has been carried out to assure safe, effectiveness and stability during storage and usage. The stem barks of Ceiba petandra and Lannea kerstingii were extracted with methanol and ethyl acetate respectively. The obtained extracts and their combinations were formulated into creams using modified Aqueous Cream BP base at concentrations ranging from 0.4 to 3.2%w/w. Physical and chemical characteristics of the creams such as stability, viscosity, pH, diffusion, irritancy and elegance were evaluated. Ketoconazole cream was used as the reference product. Creams prepared with each extract alone exhibited favorable characteristics in terms of spread ability, non-irritancy, stability and diffusivity. Creams formulated with Ceiba petandra were most stable with pH ranges of 6.21 to 7.13. Those formulated Lannea kerstingii were more acidic. Creams formulated with the combinations of the two extracts exhibited some levels of incompatibility, which increased with increasing extract concentrations. The rate of diffusion of the extracts from cream base increased with time and was generally more at 37o C as compared to that at 25o c .Cream formulations of the stem bark extracts of Ceiba petandra and Lannea kerstingii but not their combinations using modified Aqueous Cream (BP) possess satisfactory physicochemical characteristics

Evaluation of Terminalia macroptera (Combretaceae) Guill. &amp; Perr stem bark extract incorporated into an emulgel for the potential management of rheumatoid arthritis

Background: Rheumatoid Arthritis (RA) is a chronic disease which causes inflammation and damage to the joint. The goals of treatment are to stop inflammation, relieve symptoms, improve physical function and overall well-being. The purpose of this study was to evaluate Terminalia macroptera stem bark (TMB) ethanol extract and formulate it into an herbal emulgel (TME) for the potential management of RA. Methods: Phytochemical analysis and anti-inflammatory activity of TMB were first evaluated using standard analytical methods and complete Freund's adjuvant (CFA) induced arthritis model in rats respectively. Post-formulation, physical characterization of the carbopol 940 based herbal emulgels (TME) and the reduction in the induced rat paw sizes by the herbal emulgels were evaluated using diclofenac emulgel as the positive control. Results: Phytochemical screening revealed the presence of flavonoids, tannins, terpenoids, saponins, and alkaloids. Inflammatory activity of the extract gave the highest percentage inhibition with TMB (50 mg/kg). The formulated herbal emulgels had good spreadability, extrudability, pH ranging from 4.5±0.2 to 6.9±0.4 and viscosity ranging from 0.36 ± 0.20 to 8.37 ±  0.65 Pas at 6 rpm and 0.26 ±  0.01 to 10.67±0.96 Pas at 12 rpm. TME emulgel significantly (p < 0.05) reduced oedema formation and arthritic index induced by complete Freund's adjuvant in rats. TME showed dose-dependent anti-inflammatory activity comparable with commercial diclofenac emulgel. Conclusion: TMB showed an excellent inhibitory activity on the induced paw of the test animals which makes it a suitable candidate in a topical herbal emulgel formulation (TME) for the potential use in the management of RA