Development and Validation of a New Reversed Phase HPLC Method for the Quantitation of Azithromycin and Rifampicin in a Capsule Formulation.

This research aimed to develop a new method for simultaneously estimating the presence of azithromycin (AZT) and rifampicin (RIF) in a capsule formulation using reverse-phase high-performance liquid chromatography. The developed method utilized a Gemini column with a 60:40% v/v acetonitrile and potassium dihydrogen phosphate mobile phase, a flow rate of 1 mL/min, and an injection volume of 20 µL. The detection wavelengths of 210 and 254 nm for AZT and RIF, respectively, were used. Validation ensures specificity with a peak purity index > 0.99999 for AZT and >0.99995 for RIF, affirming unambiguous analyte detection. The system suitability test, within acceptable limits, validates method reliability. Linearity calibration curves (R2 = 0.998) cover a 25-150% target concentration range. Accuracy studies employing the standard addition method yield recovery values between 96.6 and 103.9% for both drugs, confirming method accuracy. Precision studies reveal % relative standard deviation values consistently below 2%, highlighting reproducibility. Robustness testing supports method reliability under varying conditions. Application to a pharmaceutical capsule formulation demonstrates the method's practicality, accurately quantifying AZT (98.30%) and RIF (99.37%). This study provides a validated analytical approach for simultaneous quantification in commercial pharmaceutical products containing both drugs, enhancing pharmaceutical quality control for critical antibiotics in complex formulations.

A Robust HPLC Approach for Quantitation of Camptothecin in Mesoporous Silica Nanoparticles Matrix and in the Presence of Its Degradation Products.

BACKGROUND: Camptothecin is a potent anti-cancer drug used for the treatment of various cancers. OBJECTIVE: The goal of this research investigation was to develop and validate a new stability indicating HPLC technique for the quantitative assessment of camptothecin in in-house developed mesoporous silica nanoparticles, a novel nanoformulation matrix for the treatment of cancer. METHOD: The Waters Inertsil® HPLC column (C18) was used for the chromatographic separation, with a flow rate of 1 mL/min, a column oven temperature of 40 °C, an injection volume of 10 µL, a detection wavelength of 216 nm, and a 10 min runtime overall. An isocratic blend of phosphate buffer (10 mM, pH7.0) and acetonitrile (60:40 v/v) served as the mobile phase. Various stress conditions including acid, alkali, oxidative, photolytic, thermal, and humidity environments were tested for the quantitative estimation of the camptothecin through the proposed method. RESULTS: The results demonstrated that the proposed method is specific (peak purity ≥ 0.999), accurate (99.69-100.64% w/w), precise (%RSD < 2.0), and sensitive (LOD-0.17 µg and LOQ-0.56 µg) in accordance with ICH guideline Q2(R1). Any unidentified degradation products did not interfere with the drug's estimation. Furthermore, the current method of analysis has eliminated any excipient interference from the matrix effect caused by the numerous excipients of the formulation matrix. CONCLUSIONS: To quantify camptothecin for routine assay purposes, this research work offers a novel and straightforward HPLC methodology with optimized chromatographic parameters, contributing to the research and development community while ensuring an appropriate and efficient use of the drug through a variety of nanoformulation for cancer treatment. HIGHLIGHTS: Stability-indicating HPLC method was found to be specific and suitable for routine analysis of camptothecin. The absence of any interference from excipients was confirmed by forced degradation studies.

Apolipoprotein E3 functionalized lipid-drug conjugated nanoparticles of Levetiracetam for enhanced delivery to the brain: In-vitro cell line studies and in-vivo study.

A significant portion of brain-tumor patients suffer from 'brain-tumor-related epilepsy (BTE)' which results in depression, anxiety and hampered quality of life. Conventional anti-epileptic drugs indicate negative interaction with other drugs augmenting the poor outcome of overall therapy. Levetiracetam (LVM) has evidenced effectiveness for BTE but its hydrophilicity restricts the passage into blood-brain barrier. The majority of lipid nanoparticles fails to load hydrophilic drug sufficiently. Therefore, lipid-drug conjugates (LDC) were synthesized using stearic acid via amide bond formation confirmed by FTIR and NMR. The nanoparticles of synthesized LDC were prepared by solvent injection method followed by functionalization with Apolipoprotein E3 (ApoE3@LDC-NP). The nanoparticles were characterized by DSC, XRD, particle size (131.6 ± 1.24 nm), zeta potential (-15.6 ± 0.09 mV), and for storage stability. In-vitro release study indicated initial burst release of 20 ± 0.63 % followed by sustained release up to 30 h (66 ± 1.40 %) for ApoE3@LDC-NP. The cell-line study on HEK293 indicated no significant cytotoxic effect and greater cell uptake through U87MG cell line. The pharmacokinetic and bio-distribution study indicated 2.5-fold greater brain-targeting of ApoE3@LDC-NP as compared to LVM solution. It proved safe in the haemolysis study and exhibited the absence of tissue necrosis. Thus, ApoE3@LDC-NP might be a promising approach for effective brain-targeting of LVM for improved clinical response in BTE.

Nanoemulsion-Based Strategy for Maximizing Nitrofurantoin Absorption: In-vitro and In-vivo Investigations.

BACKGROUND: The main objective of the current research work is to improve the absorption of Nitrofurantoin (NFT) by minimizing gastrointestinal (GI) intolerance and variations in its absorption by formulating the drug into a nanoemulsion (NE). METHOD: Based on the highest saturation solubility of NFT, soybean oil, transcutol HP, and labrafil M1944CS were selected as oil, co-surfactant, and surfactant, and a Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size, highest zeta potential, and higher drug release and hence was selected for further evaluation. RESULT: Optimized formulation (NF5) showed improved membrane permeability against pure drug suspension (2.30 times) and marketed suspension formulation (1.43 times). NF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. The relative bioavailability of NFT-NE was enhanced by 1.10 and 1.17 times compared to the marketed and pure drug suspension, respectively. CONCLUSION: Thus, it can be concluded that the optimized nanoemulsion formulation of NFT exhibited improved membrane permeability, comparable cell viability, and increased relative bioavailability. These findings suggest the potential of the nanoemulsion approach as a strategy to overcome the variability of oral absorption and GI intolerance of NFT.

Nasolabial Flap: Versatile Flap for Basal Cell Carcinoma Nose.

Nasolabial flap is very versatile flap for the lesion of basal cell carcinoma of nose. It is preferred choice for the closure of surgical defect of nose after removing the lesion of basal cell carcinoma. This flap has very good vascularity and scar is almost invisible. The objective of this study to evaluate the suitability of nasolabial flap for the basal cell carcinoma, the survival of the flap, cosmetic appearance of the patient after the surgery and patient satisfaction. This is the case study of ten cases of basal cell carcinoma of the nose. The skin lesion was at the nasal tip, dorsum and the side of the dorsum. All the surgeries were performed by the same and first author of the article at the department of Otorhinolaryngology Sir T General Hospital Bhavnagar Gujarat. The patient age ranged from 5th to 6th decades of life. All the patients were from the coastal region of Saurashtra Gujarat. All the surgery was performed as single stage surgery. The defatting of the flap was done in all cases to match with the texture of skin of nose. The biopsy was performed in all the cases before the surgery to confirm our clinical diagnosis. The underlying cartilage was removed in all the cases to prevent the recurrence and was sent separately for the frozen and histopathology examination. The nasolabial flap survived in all the ten cases. The color and the texture of the flap matched perfectly with the adjoining skin color of nose. The scar mark of the cheek side malar flap was almost invisible. There was no trap-door deformity observed and there was good aesthetic outcome. The nasolabial flap is very reliable and versatile flap for the basal cell carcinoma sugary of nose. It can reach to almost to the all area of nose including tip of the nose. Its single stage surgery with very good aesthetic results.

Post-Thyroidectomy Hypocalcemia: Clinical Study at Tertiary Care Center.

A recent review by the American association of clinical Endocrinologist (AACE) and American College of Endocrinology discussed definations and management of post-surgical hypocalcemia. In term of post-surgical hypocalcemia a total serum calcium of less than 8.5 mg/Dl(2.125 mmol/L) or ionised calcium less than 1.15 mmol/L were considered as cut off levels. The aim of the study is to evaluate & compare 30 operated cases of thyroid surgery based on its gender, age distribution, pre-operative indication & nature of surgery, post-thyroidectomy hypocalcemia. This prospective study was conducted in the Department of Otorhinolaryngology, head, neck surgery department sir T hospital, and government medical college Bhavnagar. All patients undergoing thyroidectomy surgeries were included in the study. Data collected from the patients undergoing thyroidectomise by meticulous history taking, careful clinical examination, appropriate radiological, haematological investigations including serum calcium and serum albumin, operative findings and follow-up of the cases was done after surgery for post- in association with nature of thyroid surgery. Post-thyroidectomy transient hypocalcemia is a frequent complication which can be prevented with pre-operative preparation of patients with extreme caution and pre-operative meticulous dissection, prompt identification of parathyroids and post-operative frequent monitoring of serum calcium and early treatment can prevent significant morbidity. operative hypocalcemia. The study was conducted to know the incidence of hypocalcemia after thyroid surgery.

Analytical Quality by Design-Based Robust RP-HPLC Method for Quantitative Estimation of Pregabalin and Etoricoxib in Fixed-Dose Combination Tablet Formulation.

BACKGROUND: The Central Drugs Standard Control Organization approved a bilayered, uncoated, fixed-dosage combination tablet formulation containing pregabalin (75 mg) and etoricoxib (60 mg) in November 2019 to control prolonged back pain with neuropathic components. OBJECTIVE: This research aims to create an analytical quality by design-assisted reversed phase (RP)-HPLC method for quantifying pregabalin and etoricoxib in tablet formulation. METHODS: The best chromatographic conditions were a Phenomenex C8 column (250 × 4.6 mm, 5.6 µm) and a mobile phase of 0.35% orthophosphoric acid -acetonitrile (1 + 1, by volume). A flow rate of 1 mL/min was used with a detection wavelength of 220 nm. RESULTS: The optimized reversed phase HPLC method was successfully validated by the International Conference on Hormonization guideline Q2(R1). Moreover, the percentage assay of pregabalin and etoricoxib tablet formulation was 99.05 and 100.02% w/w, respectively, using the validated RP-HPLC method. CONCLUSION: The newly developed analytical quality by design-assisted RP-HPLC method has several advantages, including shortened analytical time (2.65 min and 7.45 min pregabalin and etoricoxib, respectively), efficient separation in terms of well-defined peaks, and a simple mobile phase combination. HIGHLIGHTS: The use of analytical quality by design principles and the design of the experiment tool allowed the detection of influential parameters critical for achieving the most favourable chromatographic conditions for accurately quantifying individual drugs using the RP-HPLC method. The compliance of the results with the ICH criteria validated the method. As a result, adopting the analytical quality by design methodology ensured the development of a more robust method that can generate consistent, dependable, and quality data throughout the process while also saving time.

Comprehending the potential of metallic, lipid, and polymer-based nanocarriers for treatment and management of depression.

The World Health Organization (WHO) ranked depression as the third leading cause of global burden of disease in 2004, and it is predicted to overtake it and move to first place by 2030. It is a mental disorder that causes significant changes in the mood and day-to-day activity of an individual. Various approaches already exist for treating depression but, none of them are completely successful in treating depression. At present, discovering a new medication or delivery mechanism that can manage depression safely and efficiently is a huge challenge. Conventional formulations used in the management of depression have drawbacks like limited penetration, frequent dosing, toxicity, patient compliance concerns as well as brain barriers which are a big hurdle for antidepressant drugs to reach the brain through conventional formulations. Nano-based formulations are gaining popularity as one of the possibilities to overcome the limitations of conventional formulations by reducing the dose and dosing frequency, increasing the efficacy as well as proving it to be safe and effective means of treating depression. This review targets the neurochemistry and pathophysiological concerns of depression, strategies and problems of conventional therapies, and also recent advances in the metallic, lipid, and polymer-based nanoformulations for a variety of antidepressants. A detailed discussion of the expediency of various nanoformulations like liposomes, nanostructured lipid carriers, solid lipid nanoparticles, ethosomes, nanocapsules, dendrimer, gold and silver nanoparticles are addressed in the current review. In essence, nanoformulations hold great promises for the treatment of depression as they provide a platform with high penetration potential, targeted transmission, and improved protection and efficacy.

Bedside Tracheostomy: Our Experience in a Tertiary Care Hospital.

Tracheostomy is the creation of a stoma at the surface of skin, which leads into trachea. In the critically ill patients, it is one of the most frequently done procedure especially in intensive care unit (ICU) for those requiring prolonged mechanical ventilation. About 24% of all patients in ICU need tracheostomy (Esteban et al. in Am J Respir Crit Care Med 161:1450-1458, 2000). Historically it had a high complication rate and so many authors suggested that it should be done only in operating room (Dayal and Masri in Laryngoscope 96:5862, 1986). A standardized procedure to reduce complications was described by Jackson (Laryngoscope 19:285-290, 1909). The aim of the study is to observe and analyze the outcome of bedside open tracheostomy, in relation to its safety, complications and simplicity. Study consists of 200 patients who underwent bedside tracheostomies in a tertiary care center from 2014 to 2017 in medical/surgical/paediatric ICU's. All the procedures followed a standard protocol. In all the surgeries, two E.N.T. surgeons were scrubbed and did the procedure, assisted by two ICU nurses. One anesthetist who administered sedation and monitored the patient. If coagulation disturbances were present in elective case then they were corrected prior to the procedure. We all want the latest, safest, simplest and cheapest available technique in medical practice. Bedside tracheostomy is one such procedure. It is better than tracheostomy in operating room for patients who need prolonged mechanical ventilation in ICU as it eliminates the need of patient transport to OR and its associated complications and also minimizing cost. Training programs need to be provided to the assisting staff for better procedural outcome.

Determination of Asenapine Maleate in Pharmaceutical and Biological Matrices: A Critical Review of Analytical Techniques over the Past Decade.

Asenapine maleate is a second-generation atypical antipsychotic agent used in the treatment of schizophrenia, a neuropsychiatric disorder. It is available as a fast-dissolving sublingual tablet to avoid extensive first-pass metabolism with higher bioavailability as compared to oral formulations. Although, the established therapeutic solutions do not sufficiently satisfy the patient's safety and efficacy needs. Thus, the core research emphasis is to investigate strategies to produce novel formulations with enhanced safety and efficacy. This necessitates the development of robust, precise, and accurate methods for quantification of asenapine maleate in different sample matrices. Given the foregoing information, the current analysis concentrates on the different analytical techniques used to assess asenapine maleate in bulk, pharmaceutical formulations, and biological specimens. Reverse-phase HPLC coupled with UV detection is a majorly (nearly 50% of papers investigated) used technique for the estimation of asenapine maleate in formulations. On the other hand, for its quantification in the biological matrix, hyphenated techniques using mass spectrometry are widely used. This critical review reveals different analytical methodologies, including spectrophotometric, chromatographic, capillary electrophoresis techniques reported from 2011 to 2020, for the measurement of asenapine maleate in various sample matrices. The information presented in this review would be useful in future research for robust analytical method development for asenapine maleate utilizing a more scientific and risk-based approach. Also, it would aid to minimize analytical failure as well as method fine-tuning throughout the product life cycle. Further, this review may also direct scientists toward the development of methodologies for green research.

Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route: Ex vivo and nail clipping studies.

The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul® MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol® (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol® P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudo-ternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol® 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36±12.90µgcm-2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

Polyethylene oxide and its controlled release properties in hydrophilic matrix tablets for oral administration.

Polymers are excipients that modify the rate of drug release from pharmaceutical dosage forms. Hydrophilic polymer-based controlled drug delivery system is more advantageous as compared to the conventional delivery system as it reduces the dosing frequency, improves therapeutic efficacy, reduces side-effects, and probably enhances patient compliance. Polyethylene oxide (PEO), a nonionic hydrophilic polymer, is one of the most widely used polymers for extending the drug release. This review mainly focuses on the PEO marketed by, but not limited to, The Dow Chemical Company under the trade name of POLYOXTM. It is commercially available polyethylene oxide polymer existing in various molecular weight and viscosity grades depending upon the application. This study essentially discusses chemistry, physicochemical properties, and the impact of formulation and processing variables on the release of drug from hydrophilic PEO matrix tablets. Moreover, it also summarizes the stability, patents, and regulatory perspectives of POLYOX that can further influence the future developments of controlled release dosage forms.

Brain targeted delivery of lurasidone HCl via nasal administration of mucoadhesive nanoemulsion formulation for the potential management of schizophrenia.

This investigation aimed to design, develop, and optimize intranasal nanoemulsion for brain targeted delivery of lurasidone hydrochloride for the management and treatment of schizophrenia. The design of experiment supported optimization of high-pressure homogenization (HPH) process was executed for the manufacturing of lurasidone loaded nanoemulsion. The nanoemulsion comprising of lurasidone hydrochloride (10 mg/mL), 20% Oilmix, 25% surfactant and, 55% aqueous phase (w/w) was processed with HPH at optimized conditions to get droplet size in the nano range. The droplet size of optimized nanoemulsion was found to be 48.07 ± 3.29 nm with a polydispersity index of 0.31 ± 0.01. The optimized translucent nanoemulsion (% transmittance of 88.56 ± 2.47) was found to be non-toxic to sheep nasal mucosa and stable for six months. The results of ex vivo diffusion study revealed the improvement in drug diffused by mucoadhesive nanoemulsion (MLNE) (1.41 × 10-4 ± 1.11 × 10-5 cm2/min) as compared to the solution (1.15 × 10-4 ± 1.35 × 10-5 cm2/min). The results of pharmacodynamic studies in mice uncover the highest inhibition of compulsive behavior (64.63%) and spontaneous locomotor activity (60.87%) shown by MLNE. This may be due to increased bioavailability in a brain, and possibly confirms the potential of nanoemulsion in targeting the brain through nasal route in the treatment of schizophrenia.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations.

Novel microemulsion-based gel formulation of tazarotene for therapy of acne.

The objective of this study was to develop and evaluate a novel microemulsion based gel formulation containing tazarotene for targeted topical therapy of acne. Psudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and co-surfactant for microemulsion formation. The optimized microemulsion formulation containing 0.05% tazarotene was formulated by spontaneous microemulsification method consisting of 10% Labrafac CC, mixed emulsifiers 15% Labrasol-Cremophor-RH 40 (1:1), 15% Capmul MCM, and 60% distilled water (w/w) as an external phase. All plain and tazarotene-loaded microemulsions were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profiles of tazarotene through rat skin from optimized microemulsion formulation followed the Higuchi model for controlled permeation. Microemulsion-based gel was prepared by incorporating Carbopol®971P NF in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of tazarotene indicating its potential in improving its topical delivery. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.

Recent Survey on Patents of Nanoemulsions.

BACKGROUND: Colloidal systems are most prominent delivery systems mainly used as vehicles for the transportation, targeting the various types of biomolecules, proteins, peptides, synthetic medicinal agents. OBJECTIVE: To provide concise information on patents that are directly or indirectly related to the nanoemulsions. METHODS: The ample of research work going on with such system, in which small insoluble particle/droplets are dispersed within the immiscible secondary liquid referred to as continuous phase, is enormous. A highly praised colloidal system is nanoemulsion which possesses 'nano' sized droplets of one phase dispersed within second continuous phase. RESULTS: The characteristic features of nanoemulsion are their optical clarity, clear or bluish tint appearance and small globule size (20-200 nm) which makes them insensitive to gravitational instability, dilution and temperature. Above of all, achieving said properties using lower surfactant concentration and by supplying external energy differentiate them from microemulsion, which uses higher amount of surfactant thereby making them toxic for human body. Due to such variable advantages, researchers are engaged in going for the protecting their ideas in nanoemulsions by filling various patents. CONCLUSION: Patents in this review, covers various areas (types of drug delivery and applications) where nanoemulsion are used. Literature revealed that filing of patents on nanoemulsion increased tremendously during last 5 years and will increase in upcoming time as 21st century will be called as the century of nanomedicine.

Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study.

This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with (99m)Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. (99m)Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration.

The objective of this study was to develop and evaluate olanzapine (OZP) -loaded microemulsions (OZPME) for intranasal delivery in the treatment of schizophrenia. The OZPME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine - induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with technetium-99 ((99m)Tc), and biodistribution of drug in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rabbits was performed to determine the uptake of the OZP into the brain. OZPME were found clear and stable with average globule size of 23.87 ± 1.07 nm. In pharmacodynamic assessments, significant (p < 0.05) difference in parameters estimated were found between the treated and control groups. (99m)Tc-labeled OZP solution (OZPS)/OZPME/OZP mucoadhesive microemulsion (OZPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of OZPMME compared to intravenous OZPME was found to be five to six times higher signifying larger extent of distribution of the OZP in brain. Drug targeting efficiency and direct drug transport were found to be highest for intranasal OZPMME, compared to intravenous OZPME. Furthermore, rabbit brain scintigraphy also demonstrated higher intranasal uptake of the OZP into the brain. This investigation demonstrates a prompt and larger extent of transport of OZP into the brain through intranasal OZPMME, which may prove beneficial for treatment of schizophrenia.

Paliperidone microemulsion for nose-to-brain targeted drug delivery system: pharmacodynamic and pharmacokinetic evaluation.

OBJECTIVE: The objective of present study was to develop and evaluate paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the treatment of schizophrenia. MATERIAL AND METHODS: The PALI-ME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior and spontaneous motor activity) were performed using mice. All formulations were tagged with (99m)Tc (technetium). Pharmacokinetic evaluation of PALI in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging was performed in rabbits. RESULTS AND DISCUSSION: PALI-ME was found stable with average droplet size of 20.01 ± 1.28 nm. In pharmacodynamic studies, significant (p < 0.05) deference in parameters estimated, were found between the treated and control groups. (99m)Tc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo studies. Brain-to-blood ratio at all sampling points up to 8 h following intranasal administration of PALI-MME compared to intravenous PALI-ME was found to be 6-8 times higher signifying greater extent of distribution of the PALI in brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the PALI into the brain. CONCLUSION: This investigation demonstrates a prompt and larger extent of transport of PALI into the brain through intranasal PALI-MME, which may prove beneficial for treatment of schizophrenia.

Improving the isotretinoin photostability by incorporating in microemulsion matrix.

The present paper demonstrates the increased photostability of isotretinoin when loaded in microemulsion. The photodegradation of isotretinoin, in methanol and microemulsion formulation was studied under direct sun light. The photodegradation process was monitored by UV spectrophotometry. In methanol solution, isotretinoin undergoes complete photodegradation just within a few minutes of light exposure. Isotretinoin incorporated in microemulsion formulation showed an increased stability in comparison to the methanol solutions. In particular for isotretinoin, a residual concentration of 75% was still present after a light irradiance versus a residual value of just 16% measured at the same time in methanol solution. Further, degradation kinetic parameters of isotretinoin-loaded microemulsion formulation were demonstrated increase isotretinoin half-life about five-times in comparison with a methanol solution under a direct sun light.