Microsphere Formulations Research Articles

New Insights on the Burst Release Kinetics of Spray-Dried PLGA Microspheres.

Spray drying is one of the leading manufacturing methods for active pharmaceutical ingredients (APIs) owing to its rapid, single-step, and cost-effective nature. It also has the capacity to generate microspheres capable of controlled release of APIs including biomolecules and vaccines. However, one of the key challenges of spray-dried formulations especially with poly(lactic-co-glycolic acid) (PLGA)-based controlled-release injectables is burst release, where a significant fraction of the API is released prematurely within a short period of time following administration, leading to detrimental impact on the performance and quality of end products. This study uses a model API, bovine serum albumin (BSA) protein, to identify the sources of burst release that may affect the kinetics and performance of long-acting injectable microsphere formulations. Spray-dried microspheres with various formulations (i.e., variable BSA/PLGA ratios) were characterized in terms of their morphology, particle size, surface area, thermal properties, moisture content, as well as chemical compositions and their distributions to investigate the impact of spray drying on the burst release phenomenon. The results suggest that a relatively high initial release (85%) observed is mainly attributed to the protein distribution close to the particle surface. Morphology analysis provided evidence that the microspheres retained their spherical structure during the burst release phase. X-ray photoelectron spectroscopy, hard X-ray photoelectron spectroscopy, and argon cluster sputtering-assisted time-of-flight secondary ion mass spectrometry analysis suggest an enrichment of PLGA on particle surfaces with buried BSA protein. The statistically significant difference in particle size and surface area between three different formulations may be responsible for an initial variation in release but did not seem to alter the overall burst release profile. Considering the suggested source of burst release, the two-fluid spray-drying method, characterized by a single liquid feed delivering a preprepared emulsion, generated matrix-type microspheres with a surface layer of PLGA, as evidenced by surface analysis. The PLGA surface layer proved to be prone to degradation and pore formation, allowing for faster diffusion of BSA out of the microspheres, resulting in a burst release. Increasing the polymer concentration did not seem to halt this process.

Efficacy of Sustained-Release Formulation of Moxidectin (Guardian SR) in Preventing Heartworm Infection over 18 Months in Dogs Living in a Hyperendemic Area.

This study investigates the efficacy of a sustained-release (SR) moxidectin microsphere formulation in preventing canine heartworm infection over 18 months in Canary Hound dogs, a hunting breed common in the Canary Islands, which is a hyperendemic region. These dogs typically do not receive preventive treatments and act as reservoirs for the disease. This field study was conducted across 11 hunting kennels with 109 dogs living outdoors, none of whom were receiving heartworm prophylaxis, with Dirofilaria immitis prevalence ranging from 11.1% to 57.1% (average 36.7%). Among these, 20 clinically healthy, heartworm-negative dogs were randomly selected to receive a single subcutaneous injection of moxidectin SR (0.17 mg/kg body weight). Antigen and Knott's tests were performed at 6, 12, 18, and 24 months. All dogs completed the study without adverse reactions and remained heartworm-negative throughout. By the end of the study, kennel heartworm prevalence ranged from 14.3% to 46.7% (average 35.4%). A single subcutaneous dose of moxidectin SR at the recommended dosage may prevent patent heartworm infection in dogs for up to 18 months in hyperendemic regions. Further studies are required to confirm these findings. Extending the efficacy period of moxidectin could improve owner compliance, particularly among those with lower animal health awareness.

Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder.

Risperidone extended-release injectable suspension (R-ERIS; marketed as RYKINDO) is a novel immediate-release version of risperidone formulated as extended-release microspheres for biweekly intramuscular injection to treat schizophrenia in adults. The pharmacokinetics (PK) and safety of R-ERIS were evaluated in a multicenter, randomized, open-label, multiple-dose study in patients with stable schizophrenia or schizoaffective disorder. Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R-ERIS 25 mg or the comparator, a biweekly risperidone long-acting injectable (BW-RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections. The primary objective was to evaluate the relative bioavailability of active moiety (risperidone plus 9-hydroxyrisperidone) at steady state. Blood samples were analyzed for risperidone and 9-hydroxyrisperidone using a validated, specific, and sensitive liquid chromatography with tandem mass spectrometry method. Plasma concentration-time data were analyzed using non-compartmental methods. Pharmacokinetic parameters were calculated based on individual patient PK profiles. Safety was assessed using standard measures. At steady state, mean plasma concentrations of the active moiety were similar for R-ERIS and BW-RLAI. R-ERIS rapidly released risperidone after the injection without apparent lag time. Plasma active moiety levels reached steady state after the second injection of R-ERIS. The elimination of the drug was completed approximately 2weeks earlier for R-ERIS as compared to that for BW-RLAI. R-ERIS was safe and well tolerated. Overall, R-ERIS exhibited a faster onset and offset than BW-RLAI and statistical analysis of exposure parameters demonstrated bioequivalence at steady state.

Recent Advances in the Preparation of Protein/peptide Microspheres by Solvent Evaporation Method.

Protein/peptide drugs are extensively used to treat various chronic and serious diseases. The short half-life in vivo of protein and peptide as therapeutics drug limit the realization of complete effects. Encapsulating drugs in microspheres can slow the speed of drug release and prolong the efficacy of drugs. The solvent evaporation method is widely used to prepare protein/ peptide microspheres because of its facile operation and minimal equipment requirements. This method has several challenges in the lower encapsulation efficiency, fluctuant release profiles and the stabilization of protein/peptides, which researchers believe may be solved by adjusting the preparation parameter or formulation of microspheres. The article discusses the formulation parameters that govern the preparation of protein/peptide-loaded microspheres by the solvent evaporation method, which provides an overview of the current promising strategies for solvent evaporation for protein/peptide microspheres. The article takes parameter evaluation as the framework, facilitating subsequent researchers to quickly find possible solutions when encountering problems.

Preparation, Characterization and Quantification of Mangiferin in Mangiferin-loaded Microspheres

Introduction: Mangiferin shows great promise as a potent drug for a wide variety of diseases. Its low bioavailability and poor water solubility, however, restrict its therapeutic use. Methods: The aim of the study goal was to systematically design a UV-spectroscopy method for mangiferin quantification in analytical samples that is quick, easy, and very sensitive. In order to validate the method, UV spectroscopy was used to check for specificity, accuracy, precision, and linearity. The models were constructed with Design ExpertⓇ V.10 and optimised using Box- Behnken Design (BBD), a three-factor and three-level procedure. Results: The devised method demonstrated good levels of sensitivity, specificity, accuracy, and precision, according to the results. The absorbance and concentration showed a strong linear relationship in the given 5-25 μg/ml range for several wavelengths, with correlation coefficients of 0.989, 0.982, 0.905, and 0.896 at 364.5, 370, 378, and 265nm, respectively. The intraday precision was 0.788 at 364.5 nm, 0.801 at 370 nm, 0.739 at 378 nm, and 0.721 at 256 nm for the concentration of 20 μg/ml. Particle size and entrapment efficiency, two dependent variables in the microspheres formulation, were best suited by the models derived when the observed responses were fitted to the design. Microspheres had a high entrapment efficiency and were microsized. Interestingly, drug-encapsulated microspheres containing mangiferin maintained the spherical shape. Conclusion: The existence of well-resolved peaks and good recovery of mangiferin in the analytical method for analysis makes it ideal and acceptable for further use.

99mTc-labeled, tofacitinib citrate encapsulated chitosan microspheres loaded in situ gel formulations for intra-articular treatment of rheumatoid arthritis.

Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc-MS/TOFA-9 and 99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.

Quantitative analysis of loxoprofen sodium loaded microspheres comprising pectin and its thiolated conjugates: In-vivo evaluation of their sustained release behavior

Continuous use of oral NSAIDs can damage mucosal membrane, which results in decreased bioavailability and non-compliance with the therapy. But the use of sustained release drug delivery systems might offer a solution. Objective was to synthesize mucoadhesive SR microspheres by using different combinations of pectin (PEC) and its thiolated derivative (T-PEC3100) for improved loxoprofen (LS) permeation. Thiolated pectin (T-PEC) was synthesized by the esterification method using thioglycolic acid. Thiolation was confirmed by thiol group quantification and charring point determination. Further characterization was done by Fourier Transform Infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Ex-vivo mucoadhesion study was performed to confirm the improved characteristics. Microspheres (MS) were prepared using different ratios of PEC/T-PEC by solvent evaporation method and their particle size and surface morphology were evaluated. Mucus permeation study was carried out using the trans-well plate method. Sustained release behavior of prepared microspheres was investigated through the edema inhibition method in albino rats. T-PEC3100 was considered the optimum formulation for further evaluation and contained maximum thiol group content. FTIR spectra showed a characteristic peak of –SH and charring point was also changed considerably confirming the successful thiolation of PEC. SEM results showed spherical microspheres in the size range of 2–10 μm. Thiol-rich formulation of MS exhibited more than 80 % release after 12 h and maximum absorbable dose (MAD) was calculated as 400 μg % inhibition of edema in MS treated group was slowly attained initially but the reduction in inflammation was detected even after 24 h as compared to control group. Promising results from In-vivo edema inhibition study suggest the possible use of these thiolated MS in formulating sustained release formulation for arthritis.

Formulation and characterization of quercetin-loaded gelatin microspheres for drug delivery and their evaluation

Formulation and characterization of quercetin-loaded gelatin microspheres for drug delivery and their evaluation

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Development and Characterization of Olmesartan Medoxomil-Loaded Microspheres for Hypertension Management

Our aim is to develop and assess microspheres loaded with olmesartan medoxomil, the antagonist of angiotensin II receptor which is used in hypertension treatment, for their efficacy. The microspheres were fabricated through a solvent evaporation process employing eudragit L100 and chitosan as the inner phase and liquid paraffin as the outer phase. Optimization was done according to the results of entrapment efficiency and in-vitro drug release. Fourier-transform infrared (FTIR) analysis indicated negligible interaction, which clarifies the suitability of the drug and excipients. The resulting microspheres exhibited a pale yellow hue and free-flowing characteristics, as confirmed by micromeritics experiments. Scanning electron microscopy (SEM) revealed smooth and spherical microspheres. Particle size, ranging from 187.44 to 358.75 μm, increased with polymer concentration, as determined by optical microscopy. Formulation F9, with a ratio of eudragit L100 to chitosan at 7:1, demonstrated the highest drug entrapment percentage (97.82%). In-vitro release studies demonstrated a reduction in olmesartan medoxomil release with increasing polymer content, with formulation F9 sustaining release for 12 hours. Furthermore, short-term accelerated stability testing indicated the physicochemical stability of the microsphere formulations throughout the stability period.

Formulation and Characterization of Triamcinolone Acetonide Acetate-Loaded Microspheres Prepared by a Static Mixing Technique

Purpose: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier. Methods: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C. Results: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 μm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres. Conclusion: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner.

Determination of a Macromolecular Prodrug in Bulk and Microsphere Formulation by High Performance Thin Layer Chromatography

Determination of a Macromolecular Prodrug in Bulk and Microsphere Formulation by High Performance Thin Layer Chromatography

Formulation and evaluation of emulgels loaded with microspheres containing Baricitinib

The main objective of the present research work was to formulate and evaluate transdermal gel loaded with microspheres of Baricitinib to increase bioavailability and to reduce the dosing frequency and to improve patient compliance. Gel loaded with microspheres of Baricitinib was prepared by taking different ratios and grades of Carbopol polymers. The prepared formulations (F1–F9) were evaluated for pre-formulation studies, percentage yield, particle size, content Uniformity, drug content entrapment efficiency and in vitro dissolution studies. The optimized gel loaded with microspheres of F8 formulation (drug: Carbopol 974polymer in 1:1 ratio) is more effective compared to all formulations. The prepared gel showed acceptable physical properties such as particle size of (126.5 microns), percentage yield of (96.5%), content uniformity (97.8), and drug content entrapment efficiency (90.5%). In vitro dissolution studies have shown 100.1% drug release in 12 h. With the optimized formulation Baricitinib emulgels are formulated using different grades and ratios of Carbopol and optimized microsphere formulation F8. The Emulgel formulation F7 showed the acceptable results with a yield of 92.3%, Drug content (100.2%), Spread ability (13.38 g.cm/s), Viscocity (112.3 cP), pH off 6.05 and it was observed that formulation F7 showed 100.2% drug release within 12 hours. All the results show that the gel loaded with microspheres of Baricitinib can be effectively used for the treatment of viral infections like small fox.

Integrating Clinical Variability into PBPK Models for Virtual Bioequivalence of Single and Multiple Doses of Tofacitinib Modified-Release Dosage Form.

Tofacitinib is a potent, selective inhibitor of the Janus kinase (JAK) family of kinases with a high degree of selectivity within the human genome's set of protein kinases. Currently approved formulations for tofacitinib citrate are immediate-release (IR) tablets, modified-release (MR) tablets, and IR solution. A once daily MR microsphere formulation was developed for use in pediatric patients. Demonstration of bioequivalence (BE) between the 10 mg once daily (q.d.) MR microsphere formulation and 5 mg twice daily (b.i.d.) IR solution is needed to enable the exposure-response analyses-based bridging to support regulatory approval. To assess BE between MR microsphere and IR solution, an innovative approach was utilized with physiologically-based pharmacokinetic (PBPK) virtual BE trials (VBE) in lieu of a clinical BE trial. A PBPK model was developed to characterize the absorption of different formulations of tofacitinib using Simcyp ADAM module. VBE trials were conducted by simulating PK profiles using the verified PBPK model and integrating the clinically observed intrasubject coefficient of variation (ICV) where BE was assessed with a predetermined sample size and prespecified criteria. The VBE trials demonstrated BE between IR solution 5 mg b.i.d. and MR microsphere 10 mg q.d. after a single dose on day 1 and after multiple doses on day 5. This research presents an innovative approach that incorporates clinically observed ICV in PBPK model-based VBE trials, which could reduce unnecessary drug exposure to healthy volunteers and streamline new formulation development strategies.

Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres.

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

Formulation and Evaluation of Microspheres Containing Mefenamic Acid by Inotropic Gelation Method

Drugs with a narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastro retentive drug delivery system offers the advantage in prolonging the gastric emptying time. Losartan potassium is prescribed to treat hypertension. The current study was projected to prepare a Losartan potassium gastro retentive drug delivery system (GRDDS) of floating tablets was planned to enhance the gastric residence time, thus prolong the drug release. Losartan potassium effervescent floating tablets were prepared by utilizing the direct impression method, using polymers such as HPMCk15, xanthan gum, microcrystalline cellulose, and Sodium carbonate, with lubricants such as magnesium stearate and talc. In the present study, sodium bicarbonate was incorporated as a gas generating agent. And combination of sodium bicarbonate and citric acid was found to achieve optimum in vitro buoyancy. Total eight formulations were designed and evaluated for pre-compression parameters known as angle of repose, bulk density, tapped density, Hausner's ratio, compressibility index, and post -compression parameters are uniformity of weight variation, hardness, thickness, friability, floating lag time, and in vitro dissolution investigation and FTIR along with DSC is carried out

Effect of PLGA raw materials on in vitro and in vivo performance of drug-loaded microspheres.

Poly(lactide-co-glycolide) and poly(lactic-co-glycolic acids) (PLGAs) play a critical role in the development of commercial long-acting injectable microsphere formulations. However, very little information is available describing the impact of PLGA manufacturer and monomer distribution along the polymer chain (e.g., glycolic blockiness (Rc) and average lactic block length (LL)) on the degradation and release behavior of PLGA drug carriers in vitro and in vivo. Here, we compared the in vitro and in vivo performance of (a) four leuprolide-loaded microsphere formulations prepared from similar low-molecular-weight acid-capped PLGAs (10-14 kD, i.e., Expansorb® DLG 75-2A, Purasorb® PDLG 7502A, Resomer® RG 752H and Wako® 7515) and (b) two triamcinolone acetonide-loaded (Tr-A) microsphere formulations from similar medium-molecular-weight ester-capped PLGAs (i.e., Expansorb® DLG 75-4E and Resomer® RG 753S). Lupron Depot® and Zilretta® were used as reference commercial products. The six 75/25 PLGAs displayed block lengths that were either above or below values expected from a random copolymer. Drug release and polymer degradation were monitored simultaneously in vitro and in vivo using a cage implant system. The four leuprolide-loaded formulations showed similar release and degradation patterns with some notable differences between each other. Microspheres from the Expansorb® polymer displayed lower LL and higher Rc relative to the other 3 PLGA 75/25 microspheres, and likewise exhibited distinct peptide release and degradation behavior compared to the other 3 formulations. For each formulation, leuprolide release was erosion-controlled up to about 30% release after the initial burst followed by a faster than erosion release phase. In vitro release was similar as that in vivo over the first phase but notably different from the latter release phase, particularly for the most blocky Expansorb® formulation. The Purasorb® and Wako® formulations displayed highly similar performance in release, degradation, and erosion analysis. By contrast, the two ester-capped Expansorb® DLG 75-4E and Resomer® RG 753S used to prepare Tr-A microspheres shared essentially identical LL and higher Rc and behaved similarly although the Expansorb® degraded and released the steroid faster in vivo, suggestive of other factors responsible (e.g., residual monomer). The in vivo release performance for both drugs from the six microsphere formulations was similar to that of the commercial reference products. In summary, this work details information on comparing the similarities and differences in in vitro and in vivo performance of drug-loaded microspheres as a function of manufacturing and microstructural variables of different types of PLGA raw materials utilized and could, therefore, be meaningful in guiding the source control during development and manufacturing of PLGA microsphere-based drug products. Future work will expand the analysis to include a broader range of LL and higher Rc, and add additional important formulation metrics (e.g., thermal analysis, and residual monomer, moisture, and organic solvent levels).

Formulation and evaluation of pioglitazone microspheres

The current study focuses on the formulation, development, and in vitro testing of pologlitazone microspheres containing guar gum and chitosan as naturally occurring polysaccharides that delay release. Nine formulations were created by altering the chitosan and guar gum ratios, using span-85 as an emulsifier as well as glutaraldehyde as a chemical cross linking agent. The microspheres were assessed in terms of particle size, encapsulation effectiveness, drug loading capacity, and in vitro drug release tests. The average particle size ranged from 30.2 mm (PP 1) to 36.5 mm (PP 2). There was a range of 0.45 to 0.78 in the swelling index. Microspheres smooth surfaces were found by SEM investigation. In order to verify that there are no chemical interactions between the medication and the polymer and to understand the structure of microspheres, differential scanning calorimetry as well as Fourier transform infrared spectroscopy were employed. At 10 hours, the optimised batch PP 1 released 97.45% using phosphate buffer pH7.4 as a dissolving media. In terms of release kinetics, the optimised formula's data were best fitted with the Higuchi model (r2= 0.671) and demonstrated zero order release (r2= 0.980) via a non-Fickian diffusion mechanism.

Oral pH triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part I: Optimization, in-vitro, and ex-vivo characterization

The primary goal of this research was to investigate pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLM) using Eudragit S-100 as a pH-dependent polymer. The formulation was optimized using the Box-Behnken design. The suggested C-SKLM formulation with the amount of ketoprofen = 189.09 mg, the amount of Eudragit-100 = 600 mg, and the paddle speed = 400 rpm showed a considerable particle size (106 µm), drug encapsulation efficacy (79.67%), and % cumulative drug release at 5th hr (8.62) and 10th hr (92.62) for oral administration. Microphotographs of scanning electron microscopy indicated that the optimized C-SKLM was smooth and spherical. The differential scanning calorimetry and X-ray powder diffraction studies have shown that ketoprofen was dispersed in the polymer in its optimized C-SKLM formulation, and the spectra from the Fourier transform infrared study have shown no significant drug-polymer interaction. Ex-vivo permeation studies on isolated rat gastro-intestinal segments revealed that the maximum amount of ketoprofen permeated after 2 h through the isolated stomach (0.559 ± 0.049 mg), small intestine (1.36 ± 0.226 mg), and colon (0.972 ± 0.068 mg) was observed for ketoprofen pure. In contrast, a significantly lesser amount of the drug was permeated through the stomach (0.1 ± 0.025 mg) and small intestine (0.28 ± 0.1 mg) than the colon (0.697 ± 0.23 mg) from the ketoprofen-loaded microspheres formulation. In-vitro and ex-vivo permeation studies suggest that the developed C-SKLM could be helpful for the effective management of early morning symptoms due to rheumatoid arthritis by delaying the release by targeting the colon.

Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients with acquired immunodeficiency

Cryptococcal meningitis is a deadly disease with few treatment options. Its incidence is still high and closely linked to the HIV/AIDS epidemic. This study aimed to develop a mucoadhesive microsphere delivery system for fluconazole for the intranasal route. Microspheres of mucoadhesive fluconazole formulation variables such as different amounts of drug concentration and polymer concentration were prepared by a simple emulsion-crosslinking method.The prepared microspheres' surface was characterised by SEM (Scanning electron microscopy) and evaluated for particle size, entrapment efficiency, production yield, infrared spectroscopic study, in-vitro muco-adhesion, and in-vitro drug release. The results showed that formula 1 is the optimal mucoadhesive microsphere preparation, with a particle size of 56.375m, a spherical surface shape, an entrapment efficiency of 99.96%, and a greater mucoadhesive capability during 6-hour evaluation. Furthermore, wash-off examination revealed that the mucoadhesive ability of this delivery system has a long duration and may release the active material at the right time. The result of the researches suggesting that the formulation of mucoadhesive microspheres of fluconazole could be used to treat cryptococcal meningitis infection in HIV/AIDS patients.