The effect of processing variables on the mechanical and release properties of tramadol matrix tablets incorporating Cissus populnea gum as controlled release excipient.

BACKGROUND: Natural gums are polymers widely used as excipients in drug formulation. Polymer extraction and formulation processing methods could significantly affect formulation characteristics. OBJECTIVES: To evaluate different methods of gum extraction and the effect of different compression methods on the mechanical and release properties of tramadol hydrochloride matrix tablets incorporating cissus gum as controlled release polymer. MATERIAL AND METHODS: Water (CW) and acetone (CA) extracts of cissus gum were obtained from Cissus populea stem and two methods - wet granulation and direct compression - were used to compress the tablet and compare it with xanthan gum (X) formulations. Crushing strength and friability were used to assess mechanical properties while dissolution rate were used to assess release properties. Data were analysed using t-test and ANOVA at p < 0.05. RESULTS: The crushing strength of tramadol tablets has increased together with the increase in polymer concentration in all formulations, while friability has decreased for both methods. Tablets made by wet granulation had higher crushing strength than those made by direct compression method. The release mechanism for both direct compression and wet granulation methods was Fickian and non-Fickian respectively. The rank order for t25, t50 and t75 for all formulations was X > CA > CW. Generally, wet granulation method decreased the rate of tramadol release more than direct compression method, indicating a higher drug retarding ability. CONCLUSIONS: Incorporation of cissus gum controlled the release of tramadol hydrochloride from the matrix tablets. Extraction method and formulation variables influenced mechanical and release properties of the tablets. Cissus gum acetone extract had comparable release properties with xanthan gum and could serve as a cheaper alternative in controlled release tablet formulations.

SARS-CoV-2 Omicron spike glycoprotein receptor binding domain exhibits super-binder ability with ACE2 but not convalescent monoclonal antibody.

SARS-CoV-2, the causative virus for COVID-19 has now super-mutated into the Omicron (Om) variant. On its spike (S) glycoprotein alone, more than 30 substitutions have been characterized with 15 within the receptor binding domain (RBD); It therefore calls to question the transmissibility and antibody escapability of Omicron. This study was setup to investigate the Omicron RBD's interaction with ACE2 (host receptor) and a SARS-CoV-2 neutralizing monoclonal antibody (mAb). In-silico mutagenesis was used to generate the Om-RBD in complex with ACE2 or mAb from the wildtype. HDOCK server was used to redock and score the mAbs in Om-RBD bound state relative to the wildtype. Stability of interaction between all complexes were investigated using all-atom molecular dynamics (MD). Analyses of trajectories showed that Om-RBD has evolved into an efficient ACE2 binder, via pi-pi (Om-RBD-Y501/ACE2-Y41) and salt-bridge (Om-RBD-K493/ACE2-Y41) interactions. Conversely, in binding mAb, it has become less efficient (Center of mass distance of RBD from mAb complex, wildtype ≈ 30 Å, Omicron ≈ 41 Å). Disruption of Om-RBD/mAb complex resulted from loose interaction between Om-RBD and the light chain complementarity-determining region residues. Omicron is expected to be better transmissible and less efficiently interacting with neutralizing convalescent mAbs with consequences on transmissibility provided other mutations within the S protein similarly promote cell fusion and viral entry.

Characterizations of Alpha-Cellulose and Microcrystalline Cellulose Isolated from Cocoa Pod Husk as a Potential Pharmaceutical Excipient.

Cellulose is a non-toxic, bio-degradable, and renewable biopolymer which is abundantly available in nature. The most common source of commercial microcrystalline cellulose is fibrous wood pulp. Cellulose and its derivatives have found wide commercial applications in the pharmaceutical, cosmetic, food, paper, textile, and engineering industries. This study aims to isolate and characterize cellulose forms from cocoa pod husk (CPH) and to assess its mechanical and disintegration properties as a direct compression excipient in metronidazole tablets. Two isolated cellulose types (i.e., cocoa alpha-cellulose (CAC) and cocoa microcrystalline cellulose (C-MCC)) were compared with avicel (AV). CAC and C-MCC were characterized for their physicochemical properties using Scanning Electron Microscopy (SEM), FTIR spectroscopy, Differential Scanning Calorimetry (DSC), and X-Ray Powder Diffraction (XRD). Metronidazole tablets were produced by direct compression with cellulose. The mechanical and disintegration properties of the tablets were evaluated. CAC and C-MCC yield was 42.3% w/w and 38.25% w/w, respectively. Particle diameters were significantly different with CAC (282.22 µm) > C-MCC (161.32 µm) > AV (72.51 µm). CAC and C-MCC had a better flow than AV. SEM revealed the fibrous nature of the cellulose. FTIR and XRD analysis confirmed the presence of cellulose with crystallinity index of 69.26%, 43.83%, and 26.32% for AV, C-MCC, and CAC, respectively. C-MCC and AV are more crystalline and thermally stable at high temperatures compared to CAC. The mechanical and disintegration properties of C-MCC and AV tablets complied with pharmacopeia specifications. Taken together, C-MCC isolated from CPH displayed some fundamental characteristics suitable for use as a pharmaceutical excipient and displayed better properties compared to that of AV.

Ethnomedicinal herbs in African traditional medicine with potential activity for the prevention, treatment, and management of coronavirus disease 2019.

BACKGROUND: Ethnomedicine, a study of traditional medicine, is significant in drug discovery and development. African traditional medicine has been in existence for several thousands of years, and several drugs have been discovered and developed from it. MAIN TEXT: The deadly coronavirus disease 2019 (COVID-19) caused by a novel coronavirus known as SARS-CoV-2 has widely spread globally with high mortality and morbidity. Its prevention, treatment and management still pose a serious challenge. A drug for the cure of this disease is yet to be developed. The clinical management at present is based on symptomatic treatment as presented by individuals infected and this is by combination of more than two drugs such as antioxidants, anti-inflammatory, anti-pyretic, and anti-microbials. Literature search was performed through electronic searches of PubMed, Google Scholar, and several research reports including WHO technical documents and monographs. CONCLUSION: Drug discovery from herbs is essential and should be exploited for the discovery of drugs for the management of COVID-19. This review is aimed at identifying ethnomedicinal herbs available in Africa that could be used for the discovery and development of a drug for the prevention, treatment, and management of the novel coronavirus disease 2019.

Pharmacokinetics and saliva secretion of paracetamol in healthy male Nigerians.

A preliminary pharmacokinetic study of paracetamol was carried out in Nigerians for whom it is normal to consume paracetamol or its combination during almost any type of symptoms. After a single oral dose of 1000 mg of the drug to eight adult male volunteers, paracetamol was measured in plasma and saliva using high-performance liquid chromatography. The plasma profile showed a biexponential decline after peak absorption. Some of the pharmacokinetic parameters compared with previous results from Caucasians and Asians although some differences were observed. The absorption of paracetamol was rapid with mean tmax of 0.875 +/- 0.44 h (range, 0.5-1.5 h) and was 20 times faster than elimination rate. The Cmax varied between 11.46 and 26.44 microg mL(-1) with three of the subjects having Cmax greater than the 20 microg mL(-1) limit for therapeutic level. The elimination half-life was slightly longer than previous reports, with four subjects having t(1/2) above 3 h. The t(1/2) was found to correlate significantly (p < 0.01) with the mean residence time (MRT), an indication that MRT can be used where t(1/2) cannot be evaluated. The oral clearance was slightly lower (about 25%) than earlier reports in some Caucasians and Asians. The absorption parameters from saliva (Cmax, tmax, AUC and saliva levels) correlated well (r = 0.88 to 0.999) with those from plasma. The plasma levels were higher than saliva in all the subjects studied with variable S/P ratio of 0.64 +/- 0.1 in contrast to ealier reports of S/P ratios above unity. In conclusion, the pharmacokinetics of paracetamol in Nigerians shows possibility of higher plasma levels and slower clearance from the body.