Drop to Gate Nasal Drops Attenuates Sepsis-Induced Cognitive Dysfunction.

Nasal administration can bypass the blood-brain barrier and directly deliver drugs to the brain, providing a non-invasive route for central nervous system (CNS) diseases. Inspired by the appearance that a gate can block the outside world and the characteristics of the sol-gel transition can form a "gate" in the nasal cavity, a Drop to Gate nasal drop (DGND) is designed to set a gate in nose, which achieves protecting role from the influence of nasal environment. The DGND demonstrates the efficiency and application prospect of delivering drugs to the brain through the N-to-B. The effective concentration of single administration is increased through the hydrophobic interaction between C8-GelMA and SRT1720 (SA), and then cross-linked under UV to form nanogel, which can respond to MMP in the inflammatory microenvironment of sepsis-induced cognitive dysfunction. Finally, the SA/nanogel is compounded into the thermogel, which can respond to the nasal cavity temperature to form DGND in situ, increasing the residence time and delivery efficiency of drugs in the nasal cavity. In vitro, the DGND alleviates lipopolysaccharides (LPS)-induced BV2 inflammation. In vivo, DGND effectively targets the nasal mucosa and deliver drugs to the brain, which activate Sirt1 to alleviate inflammation mediated by microglia and improve cognitive dysfunction in sepsis mice.

Swimming short fibrous nasal drops achieving intraventricular administration.

Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus.

Chronic and allergic rhinosinusitis impacts approximately 12% of the global population. Challenges in rhinosinusitis treatment include paranasal sinus inaccessibility and variability in delivery efficiency among individuals. This study addresses these challenges of drug delivery by developing a high-efficiency, low-variability protocol for nasal drop delivery to the ostiomeatal complex (OMC) and maxillary sinus. Patient-specific nasal casts were dissected to reveal the configurations of conchae and meatus, providing insights into anatomical features amendable for sinus delivery. Fluorescent dye-enhanced videos visualized the dynamic liquid translocation in transparent nasal casts, allowing real-time assessment and quick adjustment to delivery parameters. Dosimetry to the OMC and maxillary sinus were quantified as drop count and mass using a precision scale. Key delivery factors, including the device type, formulation, and head-chin orientation, were systematically investigated in a cohort of ten nasal casts. Results show that both the squeeze bottle and soft-mist nasal pump yielded notably low doses to the OMC with high variability, and no dose from these two devices was detected within the maxillary sinuses. In contrast, the proposed approach, which included a curved nozzle surpassing the nasal valve and leveraged gravity-driven liquid translocation along the lateral nasal wall, delivered significant doses to the OMC and maxillary sinus. Iterative experimentations identified the optimal head tilt to be 40° and chin tilt to be° from the lateral recumbent position. Statistical analyses established the drop count required for effective OMC/sinus delivery. The proposed delivery protocol holds the potential to enhance chronic rhinosinusitis treatment outcomes with low variability. The dual role of nasal anatomy in posing challenges and offering opportunities highlights the need for future investigations using diverse formulations in a larger cohort of nasal models. Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus.

Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial.

Objective: Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial. Methods: A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops. Results: In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) (p = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group (p = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves. Conclusion: Lentinan nasal drops are tolerated well and can shorten the time of virus clearance.

Effect of esketamine nasal drops on pain in children after tonsillectomy using low temperature plasma ablation.

Objective: To explore the effect of esketamine nasal drops on pain in children after tonsillectomy using low-temperature plasma ablation. Methods: 76 children who underwent tonsillectomy between May 2020 and July 2021, were randomly divided into two groups of 38 cases each. Patients in the control group were treated with conventional medication, while those in the study group were treated with esketamine nasal drops, along with the routine drug treatment. Pain levels of children in the two groups were compared within 1-3 days post-surgery, and the pseudomembrane formation and shedding-off time and recovery time were statistically analyzed. Results: The pain level of children in the study group was lower than that of the control group 1-3 days post-surgery. The pseudomembrane formation and shedding-off time and recovery time in the study group were shorter than in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups, and there were no serious adverse reactions in the two groups (P > 0.05). Conclusion: It is safe to use esketamine nasal drops in children after tonsillectomy using low temperature plasma ablation, and this is found to reduce pain and shorten the recovery time.

Intervention effects and mechanism of Compound yu ’e nasal drops on allergic rhinitis in rats / 中国药房

OBJECTIVE To study the intervention effects and mechanism of Compound yu ’e nasal drops on ovalbumin induced allergic rhinitis in rats . METHODS The allergic rhinitis model of rat was induced with ovalbumin . Model rats were randomly divided into model group ，triamcinolone acetonide group （positive control ，0.026 mg/kg），Compound yu ’e nasal drops high-dose，medium-dose and low -dose groups （134.4、67.2、33.6 mg/kg），12 rats in each group . Another blank control group was set. Except for blank control group ，the corresponding drugs were given by nasal drip twice a day for 14 days. One hour after last administration，the nasal symptom scores of rats were recorded ；the levels of serum immunoglobulin E （IgE），interleukin-2（IL- 2），IL-13 and tumor necrosis factor -α（TNF-α）were measured by enzyme -linked immunosorbent assay . The changes of nasal mucosa in rat were observed by HE staining . The expressions of TNF -α，IL-2 and IL -13 in nasal mucosa were detected by Western blot. RESULTS Compared with blank control group ，nasal symptom score and the levels of serum IgE ，IL-2，IL-13，TNF-α in model group were increased significantly （P＜0.01）；obvious pathological injury was found in nasal mucosa ，and the expressions of TNF -α，IL-2 and IL -13 protein were increased significantly （P＜0.01）. Compared with model group ，Compound yu ’e nasal drops significantly reduced the nasal symptom score ，the levels of serum IgE ，IL-2，IL-13，TNF-α to different extents ，improved pathological injury of nasal mucosa and significantly inhibited the expressions of TNF -α，IL-2 and IL -13 protein（P＜0.05 or P＜ 0.01）. CONCLUSIONS Compound yu ’e nasal drops play significant effects against allergic rhinitis in rats by regulating the balance of t ype 1 helper T cells/type 2 helper T cells ，balancing and inhibiting the secretion of inflammatory cytokines .

The Effect of Recombinant Human Interferon Alpha Nasal Drops to Prevent COVID-19 Pneumonia for Medical Staff in an Epidemic Area.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as Coronavirus disease-2019 (COVID-19), has caused the sixth world's public health emergency. Healthcare staff, as the frontline population fighting the pandemic, are exposed to a high risk of infection. Therefore, developing a protective intervention for medical staff is of significant importance. OBJECTIVE: The aim of the study was to explore the effectiveness and safety of recombinant human interferon alpha (rhIFN-α) nasal drops for the prevention of coronavirus disease 2019 (COVID-19) through administering it to medical staff. METHODS: This was a prospective open-label clinical trial with parallel intervention assignment conducted on 2944 medical staff including both doctors and nurses from Taihe Hospital, Shiyan City, Hubei Province, China from January 21, 2020 to July 30, 2020. The participants were bifurcated into two groups of low risk and high risk groups according to the level of direct exposure to COVID-19 patients. The individuals of the low-risk group received rhIFN-α nasal drops for one month in addition to first level protection, and the high-risk group received a combination of rhIFN-α nasal drops coupled with thymosin-α1 with either second or third-level protection protocol. Moreover, the new-outset of COVID-19 pneumonia diagnosed by chest computed tomography (CT), after thirty days, was the primary outcome. The adverse reactions were recorded in all participants. RESULTS: 2415 of 2944 individuals belonged to the low-risk group, while 529 to the high-risk group. There was no COVID-19 pneumonia in either of the group after thirty days. The pulmonary CT scans were negative for COVID-19 pneumonia in both the groups with no new clinical symptoms. No serious adverse event was observed during the course of the intervention. CONCLUSION: The rhIFN-α nasal drops along with augmented safeguards based on standard physical isolation could effectively protect medical staff against COVID-19 pneumonia.

Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial.

Background & objectives: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing viral load and preventing clinical progression in early COVID-19 infection. Methods: This randomized clinical trial was done with a sample size of 60. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed asymptomatic patients or those with mild COVID-19 illness [National Early Warning Score (NEWS) ≤4] were included. Patients were randomized in a 1:1 manner. Control arm (standard supportive treatment, n=30) was compared with intervention arm (n=30) of standard treatment plus CQN eye drops (0.03%) repurposed as nasal drops administered six times daily (0.5 ml/dose) for 10 days. Outcome measures were adverse events and adherence; clinical progression and outcomes were measured by NEWS; sequential RT-PCR cycle threshold (Ct) values were also noted on days 0, 3, 7 and 10. Results: Nasal CQN was associated with local irritation in seven and non-compliance in one of 30 patients. Eleven patients were excluded due to enrolment error (2 - recovered; 9 - false-positive referral), and 49 patients were analyzed as per modified intention-to-treat analysis. Clinical recovery was noted as similar with 100 per cent asymptomatic by day seven in both arms. Virological outcomes also indicated similarly improving Ct values in both arms, and similar proportion of patients transitioning to non-infectivity by day 10 (controls - 19/25; nasal CQN - 15/24). Nine false-positive patients with enrolment error and day 0 RT-PCR negative were initially uninfected but had continuing COVID-19 exposure and treatment as per randomization. Patients receiving nasal CQN (n=5) demonstrated stable Ct values from day 0 to 10, while patients with no nasal CQN (n=4) demonstrated significant dip in Ct value indicating to infection (Ct<35) and infectivity (Ct<33). Interpretation & conclusions: The present study suggests to the potential of topical nasal CQN in the prevention of COVID-19 infection if administered before the infection is established. No significant differences in clinical or virological outcome were however, demonstrated in patients with mild but established illness.

Tolerability and usability of 0.5% PVP-I gargles and nasal drops in 6692 patients: Observational study.

OBJECTIVES: STUDY DESIGN: Observational study. SETTING: Secondary care ENT Centre. METHODS: All patients attending the hospital for office ENT consultations from 15th April 2020 to 15th September 2020 were included in the study. A total of 6692 office patients were evaluated for feasibility, usability and tolerability of the 0.5% PVP-I gargles and nasal drops. RESULTS: Overall practicability of using 0.5% PVP-I gargles and nasal drops at office level was assessed in terms of feasibility and usability. Feasibility and usability was considered in terms of the ease of the dispensing method of the 0.5% PVP-I gargles and nasal drops by the health care workers to the patients prior to ENT examination. Tolerance was assessed in terms of altered taste, staining of teeth or nasal skin or irritation in the nose. None reported any serious reactions or adverse effects following use of 0.5% PVP-I. CONCLUSION: The study reports the successful feasibility and usability of 0.5% PVP-I gargles and nasal drops and bears the potential to provide benefits in preventing transmission from the patients to the health care workers and vice versa. LEVEL OF EVIDENCE: 4.

A Comparison between Mygind and Kaiteki positions in administration of drops to the olfactory cleft.

OBJECTIVES: Topical nasal steroids are a common treatment intervention for olfactory dysfunction. Penetration of topical treatment to the olfactory cleft (OC), such as nasal drops, is greatly dependent on the position of the head when the treatment is administered. We aimed to examine the penetrance of nasal drops to the OC in two different head positions: the Mygind (lying head back) position and the Kaiteki position. DESIGN AND SETTING: The specimens were firstly positioned in Mygind, and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostrils in each of the head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). PARTICIPANTS: Twelve fresh-frozen cadaver specimens. MAIN OUTCOME MEASURES: Penetration of the dye into the OC. RESULTS: The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34 (standard deviation, SD = 0.92), as compared to 1.76 (SD = 0.65) in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (P > .05). CONCLUSION: Both Mygind and Kaiteki head positions are reasonable options for patients considering topical nasal drops for olfaction impairment. The preference of one position over the other should be determined by patient's preference and comfort.

Positional Installation of Intranasal Corticosteroids in the Treatment of Chronic Rhinosinusitis: A Systematic Review of the Literature.

OBJECTIVES: First-line treatment of chronic rhinosinusitis includes topical corticosteroids aimed at decreasing inflammation of sinonasal mucosa. No guidelines exist regarding the effect of head position during administration of corticosteroids. We hypothesize certain positions enhance delivery to the paranasal sinuses, with further improvement in delivery after sinus surgery. METHODS: A systematic review of the literature was conducted using Medline Ovid, Embase, Scopus, and Cochrane databases. All studies evaluating intranasal medications administered in 2 or more head positions were included. Study population, head position(s), method/volume of delivery, and outcome metrics were recorded. RESULTS: Twenty-four studies compared head positions and their role in distribution of intranasal medication. Of 12 papers studying surgically naive subjects, 6 found improvement in delivery to specific sinonasal regions (middle meatus; lateral, superior, or posterior nasal cavity) and/or symptomatic improvement, in the lying head back (LHB) or head down and forward (HDF) positions, but only 3 reached statistical significance. Of 12 papers studying surgically altered patients, 10 found delivery improved in the HDF, LHB, and head forward 45° or 90° positions. Of 5 studies of extended frontal sinus procedures (Draf IIb/III), a majority found distribution to the frontal sinus improved with the head forward 90° position. Patients found the HDF position most uncomfortable. CONCLUSIONS: Studies found no statistically significant difference in distribution to unoperated sinuses among different head positions. A minority of studies supported the use of the LHB and HDF positions. This suggests that in surgically naive patients, intranasal corticosteroid delivery to sinonasal regions and/or symptomatic improvement may be best achieved with the sinuses positioned inferior to the delivery device. Surgery improved distribution to the paranasal sinuses regardless of head position, although tilting the head forward 90° was particularly effective in delivery to the frontal sinus after extended frontal sinus procedures.

Challenges in topical therapy of chronic rhinosinusitis: The case of nasal drops application - A systematic review.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a common health issue associated with a significant life quality impairment. Intranasal glucocorticoid is the treatment of choice both as initial therapy as well as after surgery. In contrast to nasal spray, liquid glucocorticoids in form of nasal drops have the advantage of reaching the middle and upper meatus. The efficiency of the glucocorticoid nasal drops is nevertheless strictly dependent on the head position they are being applied in. Several head positions have been described in the literature but no clear recommendation towards the best suited position exist to date. METHODS: A systematic review was completed using the PubMed database. Journal articles assessing the effect of head position on intranasal drop fluid distribution, clinical effectiveness, or factors affecting patient compliance were included. RESULTS: In total 15 publications meeting the inclusion criteria have been found, out of which 9 cover the effect of head position as a primary outcome using quantitative measures. CONCLUSIONS: The positions Lying Head Back, Lateral Head Low, and variations of those can be recommended equally at the moment. Evidence speaks against the use of the classic Head Back position because of poor clinical outcome, and against the position Head Down and Forward as initial therapeutic approach because of high discomfort. For the olfactory cleft, a new head position has been described (Kaiteki), although no comparisons to other positions exist to date.

Effectiveness of Over-The-Counter Intranasal Preparations: A Randomized Trial.

To compare the effectiveness of over-the-counter normal saline with nasal decongestant drops for the symptomatic relief of nasal congestion, and to determine if nasal drops used alone are effective in the treatment of patients suffering from nasal congestion. Prospective, randomized double blinded study. Otorhinolaryngology Outpatient Department. Patients suffering from nasal congestion and similar symptoms such as nasal discharge, dryness, crusting, sneezing, itching and loss of smell. Resolution of symptoms based on visual analog scale and objective findings on anterior rhinoscopy. Chi-square test was done for comparison between the saline and decongestant groups. Subgroup analysis was done for patients on additional medication such as antibiotics. The p value is 0.701671 for the effectiveness of saline against that of decongestant, thus no significant difference exists between them for the relief of nasal congestion. The p value is 0.007497 for those on antibiotics and those that were treated only with nasal drops, thus showing a significant difference (level of significance being p < 0.05). The effectiveness of both nasal saline and decongestant drops in bringing about relief of nasal congestion is similar, and both of them may also cause headache though the mechanism is not well understood from this study. Relief might be primarily obtained with the help of oral medication and not the use of nasal drops. Level of evidence: Single-center randomized trial, level II b.

Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders.

Introduction: A recent study reported a favorable effect of vitamin B12 injections/oral folic acid support in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. Recently, vitamin B12 nasal drops were developed as an alternative to the vitamin B12 injections. As no data are available on efficacy of this formulation, we studied vitamin B12 serum levels, the physical activity scale of the RAND-36, the number of steps on an activity meter, and the fatigue and concentration scales of the CIS20r questionnaires, before and after 3 months of treatment in ME/CFS patients. Methods and Results: Fifty-one patients completed all measurements. Forty-four were female. Mean age was 42 years, and mean disease duration was 16 years. Median vitamin B12 levels before treatment were 328 (244-429) pmol/l, and 973 (476-1,476) pmol/l after treatment. Thirty-four patients reported a favorable response to treatment. In the non-responders, only a small but significant increase in vitamin B12 levels was observed. In contrast, in responders, the number of steps, the physical activity scale of the RAND-36, and the vitamin B12 serum levels increased significantly. The CIS20r fatigue scale decreased significantly, and the CIS20r concentration scale was unchanged. Conclusions: Nasal drop vitamin B12 administration resulted in a significant increase in vitamin B12 serum levels and therefore may be effective. This pilot study suggest that the nasal drops may be used as an alternative to injections because two thirds of ME/CFS patients reported a positive effect, accompanied by an increased number of steps, improvement of the RAND-36 physical functioning scale and the CIS20r fatigue scale, and a significant increase in serum vitamin B12 levels.

On ciprofloxacin concentration in chronic rhinosinusitis.

OBJECTIVE: Considering that all the evidence indicates that chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are distinct entities, the aim of this study was to compare the concentrations obtained in plasma and in sinonasal mucosa with oral and nasal topical ciprofloxacin, in patients with and without nasal polyps, without evaluating the effectiveness of the use of an antibiotic. METHODS: Prospective clinical study with single-blind randomization. The population consisted of patients with chronic rhinosinusitis with eligible for endonasal surgery, over 18 years old. It took place between January 2010 and December 2014. A single preoperative dose of ciprofloxacin (oral or nasal topic- spray, gel or drops) was given and samples of plasma and nasal mucosa (inferior turbinate, middle turbinate, ethmoid and maxillary sinus) were collected prior to surgery. The plasma and mucosal ciprofloxacin concentrations were assayed with high performance liquid chromatography (HPLC) with fluorescence detection (FD). RESULTS: The oral ciprofloxacin achieved better mucosal concentrations but had a significant plasmatic expression in all patients. None of the topical formulations achieved measurable ciprofloxacin plasmatic levels. Among the topical formulations, the gel had the best mucosal results, despite the existence of polyposis.

Optimization of Extraction Technology for Qinhao Nasal Drops by Multi-index Comprehensive Evaluation Method / 中国中医药信息杂志

Objective To optimize extraction process of Qinhao Nasal Drops by multi-index comprehensive evaluation Method. Methods With L9(34) orthogonal design, the content of rupestonic acid, chlorogenic acid, pseudoephedrine hydrochloride, total flavonoids and extract yield were set as indexes, and extraction technology of Qinhao Nasal Drops was optimized.Results Optimum extraction technology was:12 times amount of 60% ethanol, extracted three times. Conclusion The optimized extraction technology is simple, practical, and adapt to the production needs, which can be used as the basis for reasonable development of the preparation.

Xylometazoline nasal drops induced anaphylaxis: An atypical perioperative complication.

Xylometazoline nasal drops used for nasal decongestion can have side-effect in the form of palpitation, hypertension, headache, and tremors. Anaphylaxis to xylometazoline nasal drops is a relatively unrecognized complication. We encountered a patient posted for tonsillectomy who developed serious anaphylaxis upon administration of a commercially available preparation of xylometazoline nasal drops and required aggressive management for stabilization. Further evaluation and literature search indicated toward the preservative (benzylalkonium chloride) as the cause of this adverse event.

Effect of HP-β-CD on Solubility of 1,8-Oxido-p-menthane in Volatile Oil of Magnoliae Flos and Study on the Extraction Technology of Xinzhi Nasal Drops / 中国药房

OBJECTIVE:To study the effect of HP-β-CD on solubility of 1,8-oxido-p-menthane in volatile oil of magnoliae flos,and optimize the extraction technology of Xinzhi nasal drops. METHODS:Steam distillation method was adopted to extract the volatile oil in magnoliae flos. Using the content of 1,8-oxido-p-menthane in volatile oil of magnoliae flos as index,HPLC was adopted to determine the effects of HP-β-CD with different concentration on solubility of 1,8-oxido-p-menthane in volatile oil of magnoliae flos. Using the comprehensive scores of imperatorin and extract yield as indexes,orthogonal test was used to optimize the amount of ethanol,volume fraction and extraction time in extraction technology of Xinzhi nasal drops. Verification test was car-ried out. RESULTS:50% HP-β-CD aqueous solution can improve the solubility of 1,8-oxido-p-menthane to 7.6 times. The optimal extraction technology of Xinzhi nasal drops was as follow as 10-fold 80% ethanol,extracting twice,1 h every time. In verification test,the average content of imperatorin was 0.078%(RSD=2.01%,n=3),and extract yield was 10.80%(RSD=1.85%,n=3). CONCLUSIONS:HP-β-CD shows good solubilization effect on the 1,8-oxido-p-menthane in volatile oil of magnoliae flos,and the optimized extration technology for Xinzhi nasal drops is feasible.

Optimization of the Formulation of Azelastine Hydrochloride Thermosensitive In-situ Gel Nasal Drops by Central Composite Design-Response Surface Methodology / 中国药房

OBJECTIVE:To optimize Azelastine hydrochloride (AH) thermosensitive in-situ gel nasal drops formulation. METHODS:Using poloxamer 407(P407)and poloxamer 188(P188)as excipients,AH thermosensitive in-situ gel was prepared by cold solution method. The formulation was optimized by central composite design-response surface methodology using the amount of P407 and P188(g/100 ml)as factors and phase-transition temperature as index. Binomial expression was fitted,and pre-dicted and measured values were compared. RESULTS:The correlation coefficient R2 fitted by binomial expression was equal to 0.986 5. The optimal formulation was as follows as P407 for 20.414 4%,P188 for 5.035 4%,measured value of(30.81±0.02)℃, predicted values of 31 ℃,deviation of 0.61%. CONCLUSIONS:AH thermosensitive in-situ gel nasal drops formulation is opti-mized by central composite design-response surface methodology.

Estabilidad de gotas nasales de efedrina / Stability of ephedrine nasal drops

En el presente trabajo se realizó el estudio de estabilidad de las gotas nasales de efedrina. Primero se evaluó la influencia de los agentes preservantes demostrándose la incompatibilidad del clorhidrato de efedrina y el clorobutanol, por lo que fue seleccionada la combinación de cloruro de benzalconio y edetato disódico con excelentes resultados en la efectividad de preservos. Se elaboraron tres lotes pilotos de la formulación y se les realizó los estudios de estabilidad por el método acelerado y de vida de estante, respectivamente. Durante los seis meses (estabilidad acelerada) y hasta los 24 meses (vida útil) las características organolépticas cumplieron con las especificaciones establecidas. El pH del medio se comportó de manera estable cumpliendo con los límites establecidos. El principio activo no alcanzó una degradación mayor al 5%, mostrando buena estabilidad. La concentración de los preservos cumplió con los parámetros, así como el conteo microbiano del producto terminado. La formulación envasada en frascos de vidrio ámbar de calidad hidrolítica III, de capacidad nominal 15 mL con tapa de polipropileno de 18 mm y gotero interior de polietileno de alta densidad, mostró adecuada estabilidad física, química y microbiológica durante 24 meses.

The subject of this paper is a stability study of ephedrine nasal drops. We started by assessing the influence of preservative agents in the stability of the formulation. Ephedrine hydrochloride was proven to be incompatible with chlorobutanol. This led the researchers to choose a combination of benzalkonium chloride and edetate disodium, which yielded excellent results in terms of effectiveness. Three pilot batches of the formulation were prepared, and stability studies were carried out under the accelerated and shelf-life methods. For the six-month period of the accelerated stability study and the 24-month period of the shelf-life study, organoleptic characteristics were within established acceptable limits. The pH of the medium also remained stable, within acceptable limits. The degradation of the active ingredient was not greater than 5%, which indicates good stability. The concentration of preservative agents and microbial count in the finished product were also within established parameters. The formulation was packaged in amber glass bottles of hydrolytic quality III and 15 mL nominal capacity, with an 18 mm polypropylene cap and an HDPE internal dropper, and it showed adequate physical, chemical and microbiological stability during the 24 months of the shelf life stability study.