The goal of this study was to develop and characterize an ion-activated in situ gel-forming estradiol (E2) solution eye drops intended for the prevention of age-related cataracts. Accordingly, in ...situ gelling eye drops were made using gellan gum as an ion-activated gel-forming polymer, polysorbate-80 as drug solubilizing agent, mannitol as tonicity agent, and combination of potassium sorbate and edetate disodium dihydrate (EDTA) as preservatives. The formulations were tested for the following characteristics: pH, clarity, osmolality, antimicrobial efficacy, rheological behavior, and in vitro drug release. Stability of the formulation was also monitored for 6 months at multiple storage conditions per ICH Q1A (R2) guidelines. The solution eye drops resulted in an in-situ phase change to gel-state when mixed with simulated tear fluid (STF). The gel structure formation was confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 80% of drug released in 8 hr. The formulations were found to be clear, isotonic with suitable pH and viscoelastic behavior and stable at accelerated and long-term storage conditions for 6 months. In vitro results suggest that the developed formulation is suitable for further investigation in animal models to elucidate the ability of estrogen to prevent and delay cataracts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
The bioequivalence study was conducted to compare the developed paediatric fixed‐dose combination (FDC) zidovudine/lamivudine/nevirapine (60/30/50 mg) tablet – the test formulation – with ...the combined mixture of single‐entity innovator products (reference product).
Methods
A single‐dose open‐label randomized two‐way crossover study was conducted in healthy adult African volunteers after an informed consent was obtained. The 24 volunteers, divided into two groups, were administered the products after an overnight fast on two treatment days with 14 days of washout period. Blood samples were collected for 96 h and analysed using a validated RP‐HPLC‐UV assay method. Pharmacokinetic (PK) parameters (non‐compartmental model) were assessed with WinNonlin® software. Analysis of variance (ANOVA) and FDA bioequivalence statistical criterion of 90% CI or 80% to 125% range (set at P < 0.05) of least square geometric means (LSGM) ratios of test: reference product for Cmax, AUC0–t, and AUC0–∞ were determined.
Results
ANOVA indicated that the period, sequence and formulation had no significant effect on the PK parameters (P > 0.05). The 90% CIs for all the drugs were within the 80% to 125% range.
Conclusion
The developed FDC tablet is bioequivalent to the reference product.
Background
The lipid self-emulsifying system has been advanced as a promising delivery vehicle for improving the solubility and bioavailability of artemether and lumefantrine. However, the observed ...kinetic instability (propensity of lumefantrine to rapid crystallisation from nano-scale droplets) in aqueous acid has impelled some researchers to incorporate surfactants/solubilizers in the dissolution medium prior to dissolution studies. Thus, in our present work, we sought to prepare micro/large nano-scale (> 100 nm) and yet kinetically stable lumefantrine lipid self-emulsifying system (that would not require an external drug dissolution enhancing agent in the dissolution medium) and palm kernel oil-based 100 nm kinetically stable artemether lipid self-emulsifying system with rapid emulsification time. COVID-19 and
Plasmodium falciparum
-infected Africans with previous long exposure to malaria have manifested attenuated inflammatory cytokines more than malaria-naive patients. Therefore, the ingestion of artemether-lumefantrine with enhanced solubility may further promote blunting of cytokines. Therefore, this work was aimed at preparing (< 100 nm) stable artemether and aqueous acid-stable micro/large nano-scale (> 100 nm) lumefantrine lipid self-emulsifying system destined for improved antimalarial and anti-inflammatory activities.
Results
The droplet sizes of all the liquid artemether and lumefantrine formulations were between 8.95–39.88 and 1018–4195 nm, respectively. The loading efficiency for all the formulations was, between 72.91 ± 2.89 and 100.00 ± 0.29%. All the artemether and lumefantrine batches emulsified within the range of 3.90 ± 0.69 to 12.26 ± 0.69 s. Stable and transparent emulsions were formed on aqueous dilution to 1000 ml. The percentage drug released for artemether and lumefantrine ranged from 76.25 ± 2.98 to 99.22 ± 1.61%. The solid lipid self-emulsifying systems produced, had fair and passable flow properties. Differential scanning calorimetry revealed that the solid artemether and lumefantrine lipid self-emulsifying system were amorphous. Solidification with Neusilin FH
2
or surfactant replacement with Kolliphor EL and Kollidon VA 64 fine prevented micro-or large nano-scale lumefantrine lipid self-emulsifying system from crystallisation in aqueous acid (pH 1.2). Higher antimalarial activity and remarkable anti-inflammatory effects (
P
< 0.05) favoured the lipid self-emulsifying formulations.
Conclusion
Optimal in vitro and in vivo results (enhanced antimalarial and anti-inflammatory activities) were obtained with kinetically stable lumefantrine micro/large nano-scale droplets and kinetically stable palm kernel oil-based (< 50 nm) artemether lipid self-emulsifying system droplets.
Mass vaccination has proven useful in the control of COVID-19, though vaccine rollout has met major challenges. The learning curve of this process has been valuable. This qualitative study aimed to ...assess the plan, the process and the progress of the COVID-19 vaccination rollout in Lagos, Nigeria. This study was conducted at vaccination centers in eight of the 20 Local Government Areas in Lagos State from May to July 2021 among healthcare administrators, health workers and vaccine recipients. Data were collected by conducting three key informant interviews, 24 in-depth interviews and eight focus group discussions to explore the vaccination experiences of participants and the challenges facing the vaccination plan and process. The interviews and discussions were recorded, transcribed verbatim and analyzed using the thematic approach. The four-phased plan for the vaccine rollout was clear to all the key informants because the vaccination process was preceded by training. The process was strengthened by the electronic registration system, though riddled by the frequently unstable electronic and internet data capturing. This was mitigated by a stopgap manual registration and recording of client details. Challenges in the logistics of maintaining supplies of the disposable materials required for the vaccination process were overcome by the creativity of the health professionals. Vaccine hesitancy, fueled by misinformation, myths and misconceptions about the vaccine and its side effects, played a huge role in the community response. The reported vaccine side effects were mild; fever, headaches, pain at the injection site, excessive eating and sleepiness. Though the COVID-19 vaccination process appeared to have largely made progress, the future of vaccination in Nigeria is predicated upon a bottom-up approach to programmatic planning, health education and local vaccine production. Collaborations such as public-private partnerships have the potential of boosting vaccine provision for Nigeria's large population to ensure equitable access to vaccines.
The oral delivery of drugs with a narrow absorption window in the gastrointestinal tract (GIT) is often limited by poor bioavailability with conventional dosage forms due to incomplete drug release ...and short residence time at the site of absorption. To overcome this drawback and to maximize the oral absorption of these drugs, gastroretentive systems such as mucoadhesive, high-density, expandable, and floating systems have been developed. These systems provide controlled delivery of drugs with prolonged gastric residence time. However, in humans, differences in various physiological and biological factors can affect the gastric residence time and drug-delivery behavior from gastroretentive systems. Some floating drug-delivery systems (FDDS) have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses on various physiological considerations for development of FDDS, and highlights recent technological developments including new dosage forms and their production techniques (e.g., holt-melt extrusion, melt pelletization, and pulsed plasma-irradiation processes). Alternatives to the existing in vitro compendial methods for evaluating floating dosage forms will be discussed, and a critical analysis of the existing literature on FDDS, identifying the potential areas for future research, is provided.
The purpose of this study was to evaluate the postmarket pharmaceutical equivalence, stability and bioequivalence of generic and innovator fixed dose combination products of lamivudine (3TC) and ...zidovudine (AZT) 150/300mg tablets available in Nigeria. An isocratic HPLC-UV method was developed and validated for the quantitative determination of 3TC and AZT in human plasma and pharmaceutical samples. The model independent f2 similarity factor was used to compare the dissolution profiles of the two products stored at accelerated and longterm stability conditions for 6 months. The f2 values for 3TC and AZT in both products were found to be greater than 51. Also, the tablets were stable according to the USP potency and drug dissolution criteria with more than 80% of drug dissolution in 30min indicating the pharmaceutical equivalence of the two products. The 90% confidence interval for the ratios of generic/innovator pharmacokinetic parameters for 3TC/AZT were 73.5–112.6/63.4–95.8 (Cmax); 68.5–105.6/68.0–114.8 (AUC0–t); and 64.2–106.2/80.1–120.3 (AUC0–∞) respectively. The pharmacokinetic parameters failed to fully demonstrate bioequivalence between the products. The results underscored the importance of assessing the quality of the combination drug products that would ensure the safety and efficacy of the generic drug products available in the market.
Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of ...repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR, 1H NMR spectroscopy. A 32 factorial experimental design was performed using polymer type and drug-polymer ratio as independent variables. Particle size, swelling, entrapment and time for 50% drug release (t50) were dependent variables. Contour plots showed the relationship between the independent factors and the response variables. All variables except swelling increased with drug: polymer ratio. Entrapment efficiency was generally in the rank of Bitter yam>Ethyl cellulose>Chinese yam. Repaglinide microspheres had size 50±4.00 to 350±18.10μm, entrapment efficiency 75.30±3.03 to 93.10±2.75% and t50 3.20±0.42 to 7.20±0.55h. Bitter yam starch gave longer dissolution times than Chinese yam starch at all drug-polymer ratios. Drug release fitted Korsmeyer-Peppas and Hopfenberg models. Acetylated bitter and Chinese yam starches were found suitable as polymers to prolong release of repaglinide in microsphere formulations.
Abstract
Substandard and falsified (SF) medical products pose a major threat to public health and socioeconomic development, particularly in low- and middle-income countries. In response, public ...education campaigns have been developed to alert consumers about the risks of SF medicines and provide guidance on ‘safer’ practices, along with other demand- and supply-side measures. However, little is currently known about the potential effectiveness of such campaigns while structural constraints to accessing quality-assured medicines persist. This paper analyses survey data on medicine purchasing practices, information and constraints from four African countries (Ghana, Nigeria, Sierra Leone and Uganda; n > 1000 per country). Using multivariate regression and structural equation modelling, we present what we believe to be the first attempt to tease apart, statistically, the effects of an information gap vs structural constraints in driving potential public exposure to SF medicines. The analysis confirms that less privileged groups (including, variously, those in rural settlements, with low levels of formal education, not in paid employment, often women and households with a disability or long-term sickness) are disproportionately potentially exposed to SF medicines; these same demographic groups also tend to have lower levels of awareness and experience greater levels of constraint. Despite the constraints, our models suggest that public health education may have an important role to play in modifying some (but not all) risky practices. Appropriately targeted public messaging can thus be a useful part of the toolbox in the fight against SF medicines, but it can only work effectively in combination with wider-reaching reforms to address higher-level vulnerabilities in pharmaceutical supply chains in Africa and expand access to quality-assured public-sector health services.
Rectal administration is preferred to oral and parenteral routes in paediatric population because it is relatively painless while avoiding nausea, vomiting and first pass metabolism. With emergence ...of chloroquine resistance, quinine is still one of the accepted chemotherapeutic agents against Plasmodium falciparum. The aim of this study is to develop paediatric suppositories of quinine sulphate using FattibaseTM to aid stability, adequate release, ease of administration and affordability. Physical appearance, weight uniformity, hardness, melting range, liquefaction time, drug content uniformity, FTIR and release profile of the suppositories were determined at 27.0±2.0 ᵒC and 4.0±0.5 ᵒC after 0, 1, 4 and 8 weeks. Statistical analysis was done using two-way ANOVA. FTIR analysis revealed no significant modification occurred in the chemical structure of quinine throughout storage. For suppositories stored at 27.0±2.0 ᵒC, hardness and liquefaction time increased significantly with time. Release of quinine from the fattibaseTM was sustained (quantity released at 120 min, Q120 = 52.16 - 71.16%). Storage time had significant influence (p< 0.05) on all the parameters while storage temperature significantly influenced hardness, liquefaction time, Q120 and drug content. Quinine sulphate suppositories made with fattibaseTM were stable throughout the period of study and will be suitable for peadiatric use
The colon provides drug delivery opportunities for colon-specific and systemic delivery of various therapeutic agents. Different strategies have been utilized in targeting drugs to the colon. ...Recently, integrated systems which incorporate dual mechanisms in colon targeted delivery have received a lot of attention. Of particular interest is bacteria-aided biomaterials and pH-sensitive polymeric film (BPSF) coating for colon targeted drug delivery. The major constituents of these films are polysaccharides and pH-sensitive polymers. The pH-sensitive polymer retards drug release in the stomach and small intestine, while the polysaccharide is digested by colonic enzymes. Digestion of the polysaccharides by bacterial glycosidic enzymes increases the pore density in the film to facilitate drug release. Generally, bacteria-aided biomaterials and pH-sensitive films can be applied to the delivery of most small organic molecules to the colon. The review encompasses the pharmaceutical design parameters such as film digestibility, swelling index and dry mass loss (that provide molecular mechanistic analysis of film permeability) as well as tensile strength, elastic modulus, and elongation at break (that describe the desirable mechanical properties of the films). A critical analysis of formulation, techniques for characterization of film properties and drug-release kinetics from these systems are emphasized.
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