Buccal Route Research Articles

A Review on Bigel Novel Drug Delivery System

Bigels are systems that are usually formed by mixing a hydrogel and an organogel: the aqueous phase is generally made of hydrophilic biopolymer through the organic phase comprise of a gelled vegetable oil because of the presence of an organogelator. The quantity of the gelling agent in every phase, the organogel/ hydrogel percentage, and the temperature of mixing and speed of each parameter need to be considered for bigel preparation. Bigels are chiefly beneficial drug delivery systems, which have been prepared for transdermal, buccal, and vaginal routes. Analytical studies and microscopical determination are the most reported characterization techniques. Bigel’s composition and distinguishing structure confer promising drug delivery aspects such as mucoadhesion, the capability to control drug release, and the probability of using both hydrophilic and lipophilic drugs in the same system.

Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term.

The IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full‐term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 μg followed by 50 μg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography‐tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one‐compartment nonlinear clearance model. The absorption rate constant (ka) was dependent on both route and dose of administration: buccal 25 μg 0.724 (95% confidence interval, 0.54–0.92) h−1; 50 μg 0.531 (0.37–0.63) h−1; vaginal 25 μg 0.507 (0. 2–1. 4) h−1; and 50 μg 0.246 (0.103–0.453) h−1. Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63–4.77). There was no effect of body mass index or age on apparent clearance 705 (431–1099) L/h or apparent volume of distribution 632 (343–1008) L. The area under the concentration–time curve to 4 h following the first 25 μg dose of misoprostol was 16.5 (15.4–17.5) pg h/ml for buccal and 34.3 (32.5–36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.

Medical methods for first trimester abortion.

Medical methods for first trimester abortion.

Carer preferences of route of administration of transmucosal diamorphine and willingness to take part in a randomised controlled trial: an interview study (DIPPER)

BackgroundChildren and young people are usually given liquid morphine by mouth for breakthrough pain, which can take thirty minutes to work. A faster-acting, quickly absorbed, needle-free pain medicine, that is easy to administer is needed such as transmucosal (sublingual, buccal, intranasal) diamorphine. Research evidence relating to the administration of medication for breakthrough pain in children and young people is limited. This study aims to describe the experiences and preferences of parents and/or children and young people regarding the route of administration of diamorphine, barriers and facilitators comparative to oral morphine, and participation in a randomised controlled trial.MethodsIn-depth, semi-structured interviews with parents and/or children and young people at home or hospital/hospice.ResultsThirteen interviews with: nine mothers, one father, and three sets of parents jointly. No interviews took place with a child/young person. Most families had experience of the buccal route which was effective in ease of administration and time to control pain. The intranasal route was preferred by parents irrespective of experience. Parents’ willingness for their child to take part in a trial depended on the time commitment, their child’s pain trajectory and the stability of analgesic requirements.ConclusionA randomised controlled trial of oral morphine versus transmucosal diamorphine would need to consider trial logistics, especially time commitment. Parents felt that the trial should be introduced initially by the clinical team, with written information from the research team, and sufficient time to ask questions. Patients who had discontinued oral morphine because of side effects, or those with gastrointestinal failure, should be excluded. Maintaining stability in pain management was essential to families, so the timing of the trial is a potential issue.

A randomised comparative study of sublingual and vaginal misoprostol for cervical priming before minor gynaecological procedures

This study aimed to compare the effect of misoprostol using vaginal or sublingual routes on the non-pregnant uterine cervix prior to minor gynaecological procedures. One hundred and forty women were randomised 1:1 into two groups: A and B. Group A received misoprostol 400 mcg vaginally and pyridoxine 40 mg sublingually and Group B received misoprostol 400 mcg sublingually and pyridoxine 40 mg vaginally 4 h prior to procedure. The outcomes studied were maximum size of Hegar’s dilator that could be inserted into the cervix without any resistance, ease of dilatation, need and time required for further dilatation, side effects and complications. Baseline cervical dilatation was significantly more in Group A than Group B. Need for further dilatation and time required for further dilatation were also significantly less in Group A than Group B. Thus, we conclude that vaginal misoprostol is more effective than sublingual misoprostol in cervical priming before minor gynaecological procedures. Clinical Trial Registration Number: www.ctri.nic.in; CTRI/2018/07/015080 IMPACT STATEMENT What is already known on this subject? Cervical priming has been shown to result in shorter operative time, easier mechanical dilatation, reduced incidence of complications and blood loss when used prior to surgical abortion and has been recommended as a standard practice in various national and international guidelines for safe abortion practices. Misoprostol has many advantages over other ripening agents like osmotic dilators, other prostaglandins and mifepristone. Misoprostol can be given through oral, sublingual, vaginal, buccal and rectal routes. Use of misoprostol has been found to improve cervical dilatation, reduce need of further dilatation and ease of dilatation without many complications when compared to placebo for cervical priming of non-pregnant cervix. Studies comparing vaginal and sublingual routes have shown no significant difference for cervical ripening in pregnant women. What the results of this study add? We found that vaginal misoprostol for cervical priming was more effective than sublingual misoprostol in reaching a higher baseline cervical dilatation, with reduced need and time required for further dilatation before minor gynaecological procedures, although the ease of dilatation was similar in both groups. This effect of vaginal misoprostol was more marked in premenopausal women. What the implications are of these findings for clinical practice and/or further research? The results of our study are at variance with other studies done on use of misoprostol via the vaginal or sublingual routes, and hence it is imperative that large multi-center studies be performed to bring about consensus on the topic.

Dexmedetomidine: a magic bullet on its way into palliative care-a narrative review and practice recommendations.

Dexmedetomidine is a potent adrenergic alpha-2 receptor agonist. It was first approved for sedation for mechanically ventilated patients. Being a sedative medication that is not associated with respiratory depression and holding analgesic properties fosters the interest for this drug in the palliative care field. The primary objectives of this review were to identify the key indications for the real-world use of dexmedetomidine in palliative care and other disciplines. A narrative review after extensive PubMed search was performed from 1950 to present on October 21st 2021. The language of the publications was restricted to English, German, French and Italian. (I) Current dexmedetomidine use. There is a growing body of evidence that dexmedetomidine may reduce the incidence and severity of delirium, reduce opioid-consumption and postoperative nausea in intensive care settings. It is also used to facilitate withdrawal from different substances (alcohol, opioids, heroin). Concerning safety aspects of the drug, some studies reported an increased rate of serious cardiovascular events in patients with pre-existing heart conditions due to bradycardia and arterial hypo- and hypertension. Since the drug has a main hepatic metabolism, dose reduction is mandatory in patients with hepatic impairment. (II) Dexmedetomidine and palliative care. There have been sporadic case reports about the successful use of dexmedetomidine in palliative care. Indications for symptom control included sedation for hyperactive delirium, cancer pain, opioid-induced-hyperalgesia, dystonia, cough, vomiting, shivering and dyspnea. It is mainly applied via the intravenous (i.v.), subcutaneous, but also nasal and, buccal routes. Admixture ("syringe-driver") studies showed that dexmedetomidine is compatible with morphine, hydromorphone, hyoscine and haloperidol. In 2021, a first prospective cohort study became available. Here, the authors reported promising result for dexmedetomidine use in hyperactive terminal delirium for reducing delirium intensity and agitation. Especially the unique "conscious sedation" or "awake sedation" that allows patients to arouse easily under sedation and report comfort or distress was discussed by the authors. In this review, we present the main findings for dexmedetomidine from palliative care settings and other disciplines. The potential benefits and criticalities of the drug are discussed and practical recommendations for its use are provided.

A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection.

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin-cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. Following vaccination of mice, the MVA/SdFCS vaccine induced 8-fold higher neutralizing antibodies compared to MVA/S, which expressed spike without FCS inactivation, and protected against the beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU) or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, rectum) which neutralized the homologous (WA-1/2020) and heterologous VOCs, including delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both S and N specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared to IM vaccination. Following challenge with SARS-CoV-2 delta variant, the IM route induced robust protection, BU moderate protection and the SL no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.

Current approaches in Lipidic-nanoparticle Systems for Buccal Drug Delivery

The sublingual and buccal routes of administration have significant advantages for both local and systemic drug delivery. They have shown to be an effective alternative to the traditional oral route, especially when fast onset of action is required. Drugs can be rapidly and directly absorbed into the systemic circulation via venous drainage to the superior vena cava The buccal route is considered patient friendly due to its non-invasive nature and ease of administration. Such delivery route has been used as an alternative for the delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation, such as occurs in the gastrointestinal tract. However, the drug concentration absorbed in the buccal mucosa is often low to obtain an acceptable therapeutic effect, mainly due to the saliva turnover, tongue and masticatory movements, phonation, enzymatic degradation and lack of epithelium permeation. Therefore, the encapsulation of drugs into nanoparticles is an important strategy to avoid such problems and improve their buccal delivery. Different materials from lipids to natural or synthetic polymers and others have been used to protect and deliver drugs in a sustained, controlled or targeted manner, and enhance their uptake through the buccal mucosa improving their bioavailability and therapeutic outcome. Overall, the main aim of this review is to perform an overview about the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Herein, several types of nanoparticles and delivery strategies are addressed, and a special focus on pipeline products is also given.

Novel Route of Inhaled Insulin for Diabetes Treatment

Diabetes is a chronic condition characterised by insufficient insulin secretion and hyperglycemia as a result. Microvascular and macrovascular disease are two types of diabetic complications that are affected by good diabetes management. Many diabetics rely on subcutaneous insulin injections or continuous infusions to keep their blood sugar levels under control. Insulin delivery via new routes Since the 1920s, subcutaneous insulin has been used to treat diabetes; nevertheless, despite a variety of formulations, intensive insulin therapy including many daily injections has not acquired universal clinical approval. The search for a successful, well-tolerated nonenteral method for delivering insulin began in the 1920s, and has included ocular, buccal, rectal, vaginal, and other routes. Given that insulin injection therapy is burdensome for many patients, novel insulin administration routes are of interest in the diabetes sector. The use of inhalation to administer insulin to the lungs will be discussed in this review. Inhaled insulin's safety as well as efficacy in contrast to subcutaneous insulin in diverse diabetic populations are discussed. Until recently, many researchers considered that noninvasively given insulin had too low a bioavailability to be useful in clinical practise. Inhaled insulin, on the other hand, appears to be an effective, well-tolerated, and noninvasive alternative to subcutaneous regular insulin, according to a growing body of research. Importantly, inhaled insulin has a more physiological insulin profile than injectable insulin.

Feasibility of mucoadhesive chitosan maleimide-coated liposomes for improved buccal delivery of a protein drug

Chitosan-maleimide (CSMHA) coated liposomes were developed for the buccal delivery of protein. Albumin–fluorescein isothiocyanate conjugate (FITC-BSA) was used as a protein replica to be loaded in the liposomes. The liposomes were formed by a thin-film hydration technique before being decorated with CSMHA. The mucoadhesive capability of the CSMHA-coated liposomes on the porcine buccal mucosa, the loading efficiency and loading capacity, drug release, permeation through buccal mucosa, protein integrity, the cytotoxicity on oral fibroblast cells, and biocompatibility were investigated. The liposome formulations were obtained with sizes of 35–166 nm. CSMHA-coated FITC-BSA-loaded liposomes remained on the buccal tissue to the highest extent. Moreover, CSMHA-coated liposomes provided the highest buccal permeation of FITC-BSA and were safe for normal gingival fibroblast cells and buccal tissue. Therefore, the CSMHA-coated liposomes may have the capability to improve protein delivery via the buccal route.

Examination of Effective Buccal Absorption of Salmon Calcitonin Using Cell-Penetrating Peptide-Conjugated Liposomal Drug Delivery System.

IntroductionThe buccal route has been considered an attractive alternative delivery route for injectable formulations. Cell-penetrating peptides (CPPs) are gaining increased attention for their cellular uptake and tissue permeation effects. This study was aimed to evaluate the in vitro and ex vivo permeation-enhancing effect of penetratin-conjugated liposomes for salmon calcitonin (sCT) in TR146 human buccal cells and porcine buccal tissues.MethodsPenetratin was conjugated to phospholipids through a maleimide-thiol reaction. Liposomes were prepared and sCT was encapsulated using a thin-film hydration method. Physical properties such as particle size, zeta potential, encapsulation efficiency, and morphological images via transmission electron microscopy were obtained. Cellular uptake studies were conducted using flow cytometry (FACS) and confocal laser scanning microscopy (CLSM). A cell permeation study was performed using a Transwell® assay, and permeation through porcine buccal tissue was evaluated. The amount of sCT permeated was quantified using an ELISA kit and was optically observed using CLSM.ResultsThe particle size of penetratin-conjugated liposomes was approximately 123.0 nm, their zeta potential was +29.6 mV, and their calcitonin encapsulation efficiency was 18.0%. In the cellular uptake study using FACS and CLSM, stronger fluorescence was observed in penetratin-conjugated liposomes compared with the solution containing free sCT and control liposomes. Likewise, the amount of sCT permeated from penetratin-conjugated liposomes was higher than that from the free sCT solution and control liposomes by 5.8-fold across TR146 cells and 91.5-fold across porcine buccal tissues.ConclusionPenetratin-conjugated liposomes are considered a good drug delivery strategy for sCT via the buccal route.

Noninvasive Drug Delivery System Progress in Protein and Peptide Delivery

Protein and peptide drugs have tremendous therapeutic potential, and their usage in the treatment of various severe diseases has revolutionized the fields of pharmaceuticals and biotechnology. For successful therapeutic effects, several efforts have been made to deliver protein/peptide drugs through various routes of administration. Parenteral and nonparenteral drug deliveries are regarded as significant routes of drug absorption. However, there is a need to improve nonparenteral drug delivery systems (DDSs) through subsequent routes, including buccal, pulmonary, oral, ocular, transdermal, and nasal routes to increase drug absorption effectively. The study evaluated various DDS routes proposed for the distribution of proteins and peptides in terms of both parenteral and nonparenteral delivery systems. For this purpose, numerous research articles were searched from the year 2000 to 2021 using search engines such as PubMed, Google Scholar, Medline, ISI Web of Knowledge, and Bioline International while applying different keywords such as “protein and peptide drugs,” “drug delivery systems,” “parenteral and nonparenteral routes of drug delivery,” and “physicochemical barriers.” The invasive/parenteral routes have several limitations associated with drug delivery, such as poor patient compliance and the pain and discomfort associated with these routes inconvenience in treating the pediatric population. The oral route is one of the most convenient routes of noninvasive or nonparenteral drug administration; here, no pain and discomfort arise, thus helping in maintaining higher patient compliance or acceptance. The other routes of administration of proteins and peptides through buccal, intranasal, pulmonary, transdermal, rectal, and ocular routes have also been showing successful results. The success of the therapeutics is strongly influenced by the differential delivery of the targeted antigen, the choice of targeting protein or peptide, and the drug-release characteristics of the linker used. Furthermore, there should be an improvement in nonparenteral DDSs so that the drugs might be administered appropriately.

Polymeric and electrospun patches for drug delivery through buccal route: Formulation and biointerface evaluation

IntroductionOf the various transmucosal routes which are being considered for extended and controlled drug delivery, buccal route is superior to other methods owing to high administrability and milder environment for drug absorption. In this direction, mucoadhesive buccal films of venlafaxine were fabricated using a combination of biocompatible polymers. AimThe main objective of the study was to standardize an optimized formulation of polyvinyl alcohol, sodium carboxymethyl cellulose and sodium alginate that would lead to sustained drug delivery in the form of buccal patches. MethodsVarying polymeric concentrations were utilized for the fabrication of buccal patches via solvent casting method. The physical parameters were evaluated, followed by in vitro drug release studies. The electrospun nanofibers were prepared for optimized formulations and the buccal delivery system was compared to oral and intravenous routes for absorption, distribution, and elimination during in vivo studies using venlaflaxine. ResultsThe patches had high tensile strength with uniform drug content and surface pH in the range of 6.28–6.88. The release of drug was steady witha maximum release of 89.97% at 5 h. The negative hemolytic and cytotoxicity studies with TR146 cells over a range of concentrations indicated biocompatibility of the mucoadhesive patch with human tissues. The pharmacokinetics of the buccal patch of the radiolabeled drug, 99mTc-venlaflaxine, displayed favorable release pattern. The radiolabeled patch attached to rabbit buccal mucosa displayed high retention with controlled drug release as indicated by the Cmax and T1/2 values (19.94 ng/ml and 3 h). The drug release mechanism corresponded to a pure fickian diffusion-controlled mechanism following Higuchi's model. Electrospun fibrous patch of the drug had a 10% higher drug release than solvent cast patch. ConclusionIn vitro and in vivo data indicate that the polymeric system was successfully optimized for sustained drug release for about 5 h in a continuous manner with electrospun fibrous patch showing 10% increase in drug release studies. The patches displayed ideal physical and biocompatibility characteristics. This polymeric combination can therefore be further utilized for development of novel drug delivery systems with sustained drug release pattern.

Oral morphine versus transmucosal diamorphine for breakthrough pain in children: methods and outcomes: UK (DIPPER study) consensus

ObjectivesNo randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility...

A Review on Lyotropic Liquid Crystals and Its Potential Applications

Backgraound: Novel drug delivery systems have always been of immense interest for research. Majority of the drugs suffers from solubity related constraints. Lipid based drug delivery systems provide a promising approach to address this issue.Amogst various approaches, liquid crystalline systems offers distinct advantages over other available options. It maintains the phase stablility between solid and liquid phases. Objective: Lyotropic Liquid Crystals (LLCs) have highly ordered internal structure forming capabilities thereby assisting the controlled release of a therapeutic agent of varying sizes and polarities. Methods: The present article covers the structural features of dispersed mesophases (cubosomes and hexosomes), components used to prepare various mesophases, method of preparation, characterization techniques and potential applications. Results: LLCsoffers a distinct choice for delivering hydrophobic as well as hydrophilic drug. They are also suitable for the delivery of macromolecules such as peptide and protiens through various routes of administration.Lyotropic liquid crystals are extremely versatile drug delivery systems that can be used for delivering drugs across topical, oral, buccal, pulmonary and intravenous routes. Their use in the delivery of tough to deliver drugs, hormones, peptides, biomolecules and vaccines is particularly important. Conclusion: This review discussed the composition, methods of preparation and characterization of LLCs. The LLCs offer promsing delivery choice for the drugs with lower solubility and higher toxicity.

Vaginal Mucoadhesive Drug Delivery System

Mucoadhesive drug delivery systems are delivery systems which utilize the property of bioadhesion of certain polymers which become adhesive on hydration and hence can be used for targeting a drug to a particular region of the body for extended periods of time. Many of these delivery routes, particularly those through the nasal, ocular, reproductive and gastrointestinal system, involve contact with mucosal surfaces. The gastrointestinal route has been particularly popular among medical staff and patients alike. Although convenient, unfortunately, this route can be very inefficient for a number of reasons, including too rapid transit of the drug-containing delivery system past the optimum site for absorption, which is normally the small intestine and to a lesser degree the stomach and colon. Mucoadhesive formulations use polymers as the adhesive component. Mucoadhesive drug delivery systems are available in the form of tablets, films, patches, and gels for oral, buccal, nasal, ocular, vaginal, rectal and topical routes for both systemic and local effects. This review article represents the various aspects of vaginal drug delivery system, bioadhesion mechanism, Theory of bioadhesion, factors affecting bioadhesion, various types of vaginal formulation etc.

ORAL BIOAVAILABILITY ENHANCEMENT OF PACLITAXEL USING BIOENHANCER: A REVIEW

Many new chemical entities with tremendous therapeutic potential are discovered; yet, due to poor solubility and/or membrane penetration characteristics, many of these compounds have undesirable pharmacokinetic qualities. The latter is due to the lipid-like barrier imposed by epithelial mucosal layers, which drug molecules must cross to exert a therapeutic effect. Pre-systemic metabolic breakdown of drug compounds, primarily by cytochrome P450 enzymes found in intestinal enterocytes and liver hepatocytes, is another barrier. Although the nasal, buccal, and pulmonary modes of administration bypass the first-pass effect, systemic drug distribution is still reliant on drug molecules being absorbed via mucosal surfaces. Bio enhancers (naturally derived drug absorption enhancers) have been discovered to increase the amount of unaltered drug in the systemic blood circulation by regulating membrane permeability and/or pre-systemic metabolism. This paper attempts to give an overview of natural bio-enhancers and their key modes of action for medication administration via the nasal, buccal, pulmonary, and oral routes. Injections are frequently used to administer poorly bioavailable drugs, such as large, hydrophilic therapeutics. Bioenhancers may help patients by allowing for systemic distribution of these less bioavailable medications via alternative routes of administration (i.e., oral, nasal, buccal, or pulmonary routes of administration), as well as reducing dosages of tiny molecular pharmaceuticals and so lowering treatment costs.

Efficacy of buccal versus intranasal route of administration of midazolam spray in behavior management of preschool dental patients.

To assess the efficacy of aerosolized midazolam, introduced through buccal versus intranasal mucosa in managing uncooperative children undergoing dental treatment. A crossover randomized controlled clinical trial included 36 children aged 3 to 5 years, rated I or II according to the Frankl scale and ASA I or II. Each child fulfilled the requirement of having a dental condition that needed treatment in two dental settings. They were randomly assigned to one of two groups; either buccal or intranasal aerosolized midazolam was administered at the first visit. The alternate route was implemented with a 1-week washout period in the second visit. Drug acceptance and time until optimum sedation were measured. Crying, sleeping, head resistance, and child overall behavior were assessed using modified Houpt scale. In total, 34 patients (95 %) were drowsy on optimum sedation. There was a statistically higher acceptance of buccal midazolam (P < .001). Onset of optimum sedation was more rapid for the intranasal group, with a mean of 15.50 ± 4.226 minutes (P < .001), while in the buccal group the mean was 22.97 ± 4.582 minutes. No statistical differences were recorded between the two groups in all behavior rating scales, except for crying where the intranasal group was statistically higher (P = .010). Regarding the overall behavior, there was no significant difference recorded between the two groups (P = .204). Aerosolized buccal midazolam was more tolerated by the patients. However, intranasal aerosolized midazolam had a more rapid onset of sedation. Both buccal and intranasal administrations of aerosolized midazolam are safe and effective.

A Review on Current COVID-19 Vaccines and Evaluation of Particulate Vaccine Delivery Systems.

First detected in Wuhan, China, a highly contagious coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19, spread globally in December of 2019. As of 19 September 2021, approximately 4.5 million people have died globally, and 215 million active cases have been reported. To date, six vaccines have been developed and approved for human use. However, current production and supply capabilities are unable to meet global demands to immunize the entire world population. Only a few countries have been able to successfully vaccinate many of their residents. Therefore, an alternative vaccine that can be prepared in an easy and cost-effective manner is urgently needed. A vaccine that could be prepared in this manner, as well as can be preserved and transported at room temperature, would be of great benefit to public health. It is possible to develop such an alternative vaccine by using nano- or microparticle platforms. These platforms address most of the existing vaccine limitations as they are stable at room temperature, are inexpensive to produce and distribute, can be administered orally, and do not require cold chain storage for transportation or preservation. Particulate vaccines can be administered as either oral solutions or in sublingual or buccal film dosage forms. Besides improved patient compliance, the major advantage of oral, sublingual, and buccal routes of administration is that they can elicit mucosal immunity. Mucosal immunity, along with systemic immunity, can be a strong defense against SARS-CoV-2 as the virus enters the system through inhalation or saliva. This review discusses the possibility to produce a particulate COVID vaccine by using nano- or microparticles as platforms for oral administration or in sublingual or buccal film dosage forms in order to accelerate global vaccination.

Population pharmacokinetics of oxycodone: Premature neonates to adults.

Oxycodone is used in children and adults for the control of acute postoperative pain. Covariate influences such as age, size, and fat mass on oxycodone pharmacokinetic parameters over the human lifespan are poorly quantified. Pooled oxycodone time-concentration profiles were available from preterm neonates to adults. Data from intravenous, intramuscular, buccal, and epidural formulations were analyzed using nonlinear mixed-effects models. Normal fat mass was used to determine the influence of fat on oxycodone pharmacokinetics. Theory-based allometry was used to scale pharmacokinetic parameters to a 70kg individual. A maturation function described the increase in clearance in neonates and infants. There were 237subjects (24weeks postmenstrual age to 75years; 0.44-110kg) providing 1317 plasma concentrations. A three-compartment model with first-order elimination best described oxycodone disposition. Population parameter estimates were clearance (CL) 48.6 L.h-1 .70kg-1 (CV 71%); intercompartmental clearances (Q2) 220 L.h-1 .70kg-1 (CV 64%); Q3 1.45 L.h-1 .70kg-1 ; volume of distribution in the central compartment (V1) 98.2 L.70kg-1 (CV 76%); rapidly equilibrating peripheral compartment (V2) 90.1 L. 70kg-1 (CV 76%); slow equilibrating peripheral compartment (V3) 28.9 L.70kg-1 . Total body weight was the best size descriptor for clearances and volumes. Absorption halftimes (TABS ) were: 1.1minutes for intramuscular, 70minutes for epidural, 82minutes for nasogastric, and 159.6minutes for buccal administration routes. The relative bioavailability after nasogastric administration was 0.673 with a lag time of 8.7minutes. Clearance matured with age; 8% of the typical adult value at 24weeks postmenstrual age, 33% in a term neonate and reached 90% of the adult clearance value by the end of the first year of life. Allometric scaling using total body weight was the better size descriptor of oxycodone clearance than fat-free mass.