Spray-dried Powders Research Articles

Sugarcane bagasse derived phosphorylated cellulose as substrates for potassium release induced by phosphates surface and drying methods

Encapsulation and controlled release of potassium by phosphorylated cellulose (P-cell) was systematically demonstrated by drying of aqueous P-cell suspensions with potassium chloride (KCl) in varied stoichiometric K+/Cell-O-HPO3- ratios of 1:1, 2:1, and 4:1, and dried into powder-like fibrous fluffs, paper-like films, and three-dimensional porous structures by spray-, oven-, and freeze-drying. Cellulose isolated from sugarcane bagasse as agricultural waste was optimally phosphorylated at 1:0.5:2 anhydroglucose (AHG)/(NH4)2HPO4/CO(NH2)2 as 14.6 µm wide, ca. 366 µm long, highly crystalline (72%) microfibers with 2.4 mmol g−1 charge. Oven drying led to more crystalline (73%) and thermally stable (252.1 °C) films than spray-dried powders (67%, 250.5 °C) and freeze-dried porous bulk (71%, 249.8 °C). The release of highly water-soluble KCl from these three P-cell substrates was highest from the fibrous (90.4–97.3%), three-dimensional porous structure solids (73.5–81.7%), then films (60.4–74.5%), thus could be tuned by varying the anionic/cationic loadings along with drying methods.

Impact of Different Drying Methods on Nutritional, Colour Change, Solubility and Microbial Count of Selected Herbal Plant Powders

The research aimed to study the effect of drying processes (spray and freeze drying), and feed concentrations (80%, 65% and 50% of plant in water, w/w) on physicochemical and microbiological characteristics of star gooseberry (Sauropus androgynus), ceylon spinach (Basella alba), and cowslip creeper (Telosma minor). After drying, the powder recovery of herbal plant powders was up to 77.47%. The aw and moisture content of spray-dried powder (SDP) were lower than that of freeze-dried powder (FDP). The drying method did not significantly affect nutritional values of both powders, whereas the feed concentrations markedly affected the nutritional values of the powders. The fibre and fat contents of powder prepared from 80% feed concentration had the highest values (p<0.05). The dried star gooseberry powder was rich in protein (13.01-16.81%) and fibre (5.03-5.52%). The colour of FDP represented a smaller change than that of SDP. The dried powders prepared by 80% showed the highest solubility, up to 85.44%. The microbial counts of SDP were lower than that of FDP. The colour might well have been preserved by freeze drying, whereas a low moisture and microbial count were likely due to the spray drying.

Correction: Effect of Aeration Techniques on Flow Properties of Spray-Dried Sugar Powders — Process Optimization Studies

Correction: Effect of Aeration Techniques on Flow Properties of Spray-Dried Sugar Powders — Process Optimization Studies

Encapsulation of Functional Plant Oil by Spray Drying: Physicochemical Characterization and Enhanced Anti-Colitis Activity.

In this study, an encapsulation system was developed for functional plant oil delivery. Through a series of orthogonal experiments and single factor experiments, the raw material compositions, emulsification conditions, and spray drying conditions for the preparation of flaxseed oil and safflower seed oil powders were optimized, and the final encapsulation efficiency was as high as 99% with approximately 50% oil loading. The storage stability experiments showed that oil powder’s stability could maintain its physicochemical properties over six months. Oral supplementation of the spray-dried flaxseed oil powder exhibited a significant and better effect than flaxseed oil on alleviating colitis in C57BL/6J mice. It suppressed the pro-inflammatory cell factors, including IL-6 and TNF-α, and repaired gut microbial dysbiosis by increasing the microbial diversity and promoting the proliferation of probiotic taxa such as Allobaculum. This work suggests that spray-dried flaxseed oil powder has great potential as a nutraceutical food, with spray drying being a good alternative technique to improve its bioactivity.

Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery.

While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders. Spray drying was performed using 5% lactose solution (m/V), and the targets were set to obtain nanoparticle sizes after redispersion of spray-dried powders around 150 nm, a residual moisture level below 5%, and RNA loss below 15% at maintained RNA bioactivity. The LNPs consisted of an ionizable cationic lipid which is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG encapsulating siRNA. Prior to the spray drying, the latter process was simulated with a novel dual emission fluorescence spectroscopy method to preselect the highest possible drying temperature and excipient solution maintaining LNP integrity and stability. Through characterization of physicochemical and aerodynamic properties of the spray dried powders, administration criteria for delivery to the lower respiratory tract were fulfilled. Spray dried LNPs penetrated the lung mucus layer and maintained bioactivity for >90% protein downregulation with a confirmed safety profile in a lung adenocarcinoma cell line. Additionally, the spray dried LNPs successfully achieved up to 50% gene silencing of the house keeping gene GAPDH in ex vivo human precision-cut lung slices at without increasing cytokine levels. This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections.

Ultrasound-Assisted Encapsulation of Anthraquinones Extracted from Aloe-Vera Plant into Casein Micelles.

Aloe-vera extracted anthraquinones (aloin, aloe-emodin, rhein) possess a wide range of biological activities, have poor solubility and are sensitive to processing conditions. This work investigated the ultrasound-assisted encapsulation of these extracted anthraquinones (AQ) into casein micelles (CM). The particle size and zeta potential of casein micelles loaded with aloin (CMA), aloe-emodin (CMAE), rhein (CMR) and anthraquinone powder (CMAQ) ranged between 171–179 nm and −23 to −17 mV. The AQ powder had the maximum encapsulation efficiency (EE%) (aloin 99%, aloe-emodin 98% and rhein 100%) and encapsulation yield, while the whole leaf Aloe vera gel (WLAG) had the least encapsulation efficiency. Spray-dried powder (SDP) and freeze-dried powder (FDP) of Aloe vera showed a significant increase in size and zeta potential related to superficial coating instead of encapsulation. The significant variability in size, zeta potential and EE% were related to anthraquinone type, its binding affinity, and its ratio to CM. FTIR spectra confirmed that the structure of the casein micelle remained unchanged with the binding of anthraquinones except in casein micelles loaded with whole-leaf aloe vera gel (CMWLAG), where the structure was deformed. Based on our findings, Aloe vera extracted anthraquinones powder (AQ) possessed the best encapsulation efficiency within casein micelles without affecting its structure. Overall, this study provides new insights into developing new product formulations through better utilization of exceptional properties of casein micelles.

Evaluation of spray-dried eggs as a micronutrient-rich nutritional supplement

Regular consumption of hen eggs can help to prevent deficiencies of essential nutrients, such as essential amino acids, vitamin A and E or trace elements zinc and selenium, for vulnerable populations. This study focused on assessing the nutritional value of spray-dried eggs, favored by their manufacturability, storability and ease of addition to (complementary) foods. Using a wide range of analytical techniques, we recorded and compared the nutrient profiles of commercially produced pasteurized whole eggs and their respective powder samples spray-dried at 160°C. Important nutrients that were not significantly affected by spray-drying include total fat content, several amino acids, α- and δ-tocopherol, lutein, zeaxanthin, essential trace elements and cobalamin. The most notable mean losses were found for unsaturated fatty acids, e.g., linoleic (by −38.7%, from 4.11 ± 0.45 to 2.52 ± 0.75 g/100 g DM) and linolenic acid (by −60.8%, from 0.76 ± 0.05 to 0.30 ± 0.04 g/100 g DM). Despite recording significant retinol losses in two out of three batches, the overall low reduction of −14% recommend spray-dried eggs as a valuable source of vitamin A. A daily intake of spray-dried egg powder corresponding to one medium sized egg meets dietary reference values for children, e.g., by 100% for vitamin E, by 24% for retinol, by 61% for selenium and by 22% for zinc. In conclusion, even though a dry weight comparison favors supplementation with pasteurized whole eggs, our results demonstrate a high potential for spray-dried eggs as nutritional supplement. However, the spray-drying process should be optimized toward higher retentions of unsaturated fatty acids and retinol.

Improvements in the Physical Properties of Agglomerated Milk Protein Isolate/Skim Milk Powder Mixtures Via Fluidized Bed Agglomeration

Protein-enriched dairy powder is widely consumed to promote muscle synthesis. Recently, in Korea, elderly people have also begun consuming protein powder products to prevent muscle loss. However, these protein-enriched powders have poor flowability and hydration properties because of the fine particles of spray-dried milk protein powder. Therefore, in this study, the fluidized bed agglomeration process was used to solve these problems. The rheological and physical properties of milk protein isolate (MPI)/skim milk powder (SMP) mixtures were effectively improved via fluidized bed agglomeration. The particle size of the MPI/SMP mixtures significantly increased from 35.7–58 μm to 118–136 μm, the flowability level improved from fair (21.4–26.3) to good (15.7–16.3), and the cohesiveness level changed from intermediate (1.27–1.36) to low (1.18–1.19) after fluidized bed agglomeration. In addition, the wetting time of the agglomerated MPI/SMP mixtures was effectively reduced to 4.67–58.3 s by fluidized bed agglomeration. These findings may be useful for manufacturing protein-enriched dairy powders with good instant properties.

A preliminary study on perioperative hemostatic effect of spray dried powder of <em>Chromolaena odorata</em> leaf extract

Accidents or surgery often cause internal haemorrhage in liver and arteries which may lead to patient morbidity and mortality. The current hemostatic agents used for treatment like collagen, oxidized cellulose, and chitosan suffer from side effects which include infection, inflammation and even sepsis. In the present study, we studied the spray dried powder (SDP) of the aqueous extract of the leaves of Chromolaena odorata (L.) R.M.King & H.Rob., commonly known as Siam weed or Common floss flower and also Christmas bush, for its hemostatic efficacy in two experimental models of surgery. Firstly, the SDP was screened through standard pharmacognostical parameters, and a part of the liver was lacerated in rats and femoral artery was transected in rabbits to assess the blood loss in pre-weighed gauze with and without treatment. In the liver laceration model, an effective blood loss reduction of 54.30 % was observed with oral administration of SDP 7 days prior to surgery. Similarly, application of SDP at the site of artery transection caused 70.36% reduction in blood loss as compared to the control rabbit artery. The results suggest that oral delivery and/or application of SDP of C. odorata by formulating it in a suitable drug delivery tool could minimize perioperative bleeding in hepatic and arterial tissue and improve recovery.

Microencapsulation of karonda (Carissa carandas L.) anthocyanin extracts: effects of drying conditions on antioxidant contents and activities of spray-dried powder

PurposeThis study aims to investigate the effect of spray drying temperature and maltodextrin addition on the contents of phenolics, flavonoids, anthocyanins and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging activity, ferric reducing antioxidant power and reducing power) of karonda powder.Design/methodology/approachOver the past few decades, the demands for application of natural colorants in food production have been attracting the attention of academic research and food industry. Anthocyanins, a red pigment commonly found on plants, show high potentials in the preparation of spray-dried pigment powder. This study, therefore, was conducted using full factorial design with two factors, namely, inlet temperature (150°C and 160°C) and soluble solid concentration (10, 15 and 20°Brix) with maltodextrin as carrier to produce pigment powder from karonda, an anthocyanin-rich fruit which is native to southeast Asia.FindingsIncreasing soluble solid content from 10 to 15°Brix resulted in a 42%–57% reduction in phenolic, flavonoid and anthocyanin contents. However, when increasing the amount of maltodextrin from 15 to 20°Brix, a lower reduction (approximately 11%–19%) was observed. In samples with the same °Brix, there was no significant variation in antioxidant contents and activities, especially at high maltodextrin ratios. In addition, the reducing power of samples dried at higher temperature (160°C) was higher than that of samples dried at lower temperature. Karonda spray-dried powder showed a good positive correlation (p < 0.01) between antioxidant contents and DPPH• activity.Originality/valueTo the best of the authors’ knowledge, in this study, for the first time, the effect of spray drying conditions on the quality of karonda powder was investigated.

Effect of excipient wall materials on the development of ginger oleoresin microcapsules: assessing the physicochemical, antioxidant and structural properties.

Ginger oleoresin is prone to destruction from air, light and high temperatures and has a limited shelf life if kept improperly. Its viscous and sticky characteristics also make it difficult to handle and utilize. These issues can be solved via microencapsulation. The goal of this research was to evaluate how different wall materials affect the properties of microencapsulated ginger oleoresin powder. Ginger oleoresin microcapsules were developed through spray drying technique using gum acacia (GA) and whey protein isolate (WPI) as wall materials. The characteristics of the obtained powder, including water activity, wettability and encapsulation efficiency, were evaluated, corresponded to values of 0.20, 90.54 s and 84.15% for whey protein isolate-based ginger oleoresin powder. Whey protein isolate microcapsules also exhibited higher phenolic content (27.26 mg gallic acid equivalents g-1 ), total flavonoid (2.94 mg quercetin equivalents g-1 ) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (68.71%) than GA microcapsules. Both WPI- and GA-based oleoresin microcapsules displayed poor flowability, but possessed a metastable amorphous state as indicated by X-ray diffraction. GA-encapsulated oleoresin microcapsules showed a significant increase in particle size (1983 nm) compared to WPI oleoresin microcapsules. Fourier transform infrared analysis of the developed oleoresin microcapsules indicated no change in molecular structure except for a variation in peak intensity. Whey protein isolate proved to be more efficient in maintaining the physicochemical and antioxidant activity of spray-dried ginger oleoresin powder. The present study revealed whey protein-based oleoresin powder could be used as a therapeutic agent in various nutraceutical applications. © 2022 Society of Chemical Industry.

Process Modelling, Scale-Up and Characterization of Acetaminophen Spray Dried Milk Powder as Novel Pediatric Dosage Form.

Successful drug therapy in children is contingent upon hassle-free administration of pediatric dosage forms. Pediatric patients suffer from difficulty in swallowing due to weak esophagus muscles in their early age. Considering this challenge liquid formulations are preferred over solid dosage form among pediatric patients to avoid the possibility of choking which can be a serious life-threatening condition in children. The main aim of the present research work was to develop a reconstitutable amorphous acetaminophen spray-dried milk powder (ASDM) as novel pediatric formulation. ASDM was prepared by spray drying process and the spray drying process was optimized using Box-Behnken design to study the effect of spray drying process parameters at X1 [inlet temperature], X2 [aspiration rate] and X3 [feed rate] to Y1 [% yield], Y2 [angle of repose], Y3 [Hausner's Ratio] and Y4 [Carr's Index] as dependent variables of ASDM. In addition, each batch was characterized for particle size by polarized light microscopy and drug entrapment. Predicted parameters from optimized spray drying process model were successfully employed to manufacture a scale up cum validation batch of ASDM, which showed notably improved yield and desirable flow properties. The scale-up validation batch was further characterized using thermal analysis, diffraction studies, spectroscopic analysis, dispersion studies, stability APAP in dispersion formulation and formulation stability studies to confirm the physico-chemical stability of ASDM. Thus, ASDM for oral use can serve as a promising pediatric formulation and the developed prototype formulation can be further extended to future newly discovered drugs with similar characteristics.

Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery.

The therapeutic options for severe asthma are limited, and the biological therapies are all parenterally administered. The purpose of this study was to formulate a monoclonal antibody that targets the receptor for IL-4, an interleukin implicated in the pathogenesis of severe asthma, into a dry powder intended for delivery via inhalation. Dehydration was achieved using either spray drying or spray freeze drying, which exposes the thermolabile biomacromolecules to stresses such as shear and adverse temperatures. 2-hydroxypropyl-beta-cyclodextrin was incorporated into the formulation as protein stabiliser and aerosol performance enhancer. The powder formulations were characterised in terms of physical and aerodynamic properties, while the antibody was assessed with regard to its structural stability, antigen-binding ability, and in vitro biological activity after drying. The spray-freeze-dried formulations exhibited satisfactory aerosol performance, with emitted fraction exceeding 80% and fine particle fraction of around 50%. The aerosolisation of the spray-dried powders was hindered possibly by high residual moisture. Nevertheless, the antigen-binding ability and inhibitory potency were unaffected for the antibody in the selected spray-dried and spray-freeze-dried formulations, and the antibody was physically stable even after one-year storage at ambient conditions. The findings of this study establish the feasibility of developing an inhaled dry powder formulation of an anti-IL-4R antibody using spray drying and spray freeze drying techniques with potential for the treatment of severe asthma.

The effect of plant-derived peptides on the hot-melt stickiness of herbal extracts during spray drying

The aim of this study was to explore plant-derived peptides as carrier material with the function of anti-hot-melt stickiness of traditional Chinese herbal extracts during spray drying. Crataegi fructus extract (CFE) with a severe hot-melt stickiness problem was used as a model drug, and soy peptides (SPT) were screened as the most effective and suitable carrier material among seven plant-derived proteins and peptides which include soy protein isolate, walnut protein and five kinds of peptides (corn peptides, wheat peptides, walnut peptides, rice peptides and SPT). The addition of 15% SPT also exhibited a strong anti-stickiness effect in other four hot-melt sticky herbal extracts from Chinese herbs (Lycii fructus, Corni fructus, Chaenomelis fructus and Mume fructus) since the obtained powder increased from completely sticking to the wall to more than 50% powder yield. The dynamic surface tensions (DST) of CFE decreased consistently with the increase of SPT from 5% to 20%, and DST1000ms had consistent reduction with the addition of SPT from zero to 20%. Meanwhile, the adhesive force of the single droplet at 28 min decreased below 18.5 N. The softening point of the spray-dried powder of CFE added 15% SPT increased by about 40 °C, and the addition of 15% SPT improved the stability which might be similar with the addition of 50% MD based on scanning electron microscope analysis but more efficiently. These findings confirmed that SPT plant-derived could serve as effective and stable carrier material with good anti-stickiness ability during spray drying.

Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery

Shortcomings of oral donepezil administration in the treatment of Alzheimer’s disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose-to-brain delivery, coupling careful design of chitosan and mannitol-based carrier matrix with spray-drying technology advantages and early consideration of adequate nasal administration mode, employing QbD approach. Unprecedentedly, ultrasonic nozzle was used to atomise the drying feed in response to size-related requirements for nasal aerosol particles. The optimised spray-drying process resulted in free-flowable dry powder with a great majority of particles larger than 10 µm, ensuring localised nasal deposition upon aerosolization, as evidenced by using 3D-printed nasal cavity model. QbD approach coupling formulation, process and administration parameters enabled optimisation of drug deposition profile reaching tremendously high 65.5 % of the applied dose deposited in the olfactory region. The leading formulation exhibited favourable swelling, mucoadhesion, drug release and permeation-enhancing properties, suiting the needs for efficient brain-targeted delivery. Results of in vitro biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient donepezil nose-to-brain delivery. The obtained results encourage extending the study to an appropriate in vivo model needed for the final proof-of-concept.

Effect of Aeration Techniques on Flow Properties of Spray-Dried Sugar Powders — Process Optimization Studies

Effect of Aeration Techniques on Flow Properties of Spray-Dried Sugar Powders — Process Optimization Studies

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder.

SARS-CoV-2, the causative agent of COVID-19, predominantly affects the respiratory tract. As a consequence, it seems intuitive to develop antiviral agents capable of targeting the virus right on its main anatomical site of replication. Ivermectin, a U.S. FDA-approved anti-parasitic drug, was originally shown to inhibit SARS-CoV-2 replication in vitro, albeit at relatively high concentrations, which is difficult to achieve in the lung. In this study, we tested the spray-drying conditions to develop an inhalable dry powder formulation that could ensure sufficient antiviral drug concentrations, which are difficult to achieve in the lungs based on the oral dosage used in clinical trials. Here, by using ivermectin as a proof-of-concept, we evaluated spray-drying conditions that could lead to the development of antivirals in an inhalable dry powder formulation, which could then be used to ensure sufficient drug concentrations in the lung. Thus, we used ivermectin in proof-of-principle experiments to evaluate our system, including physical characterization and in vitro aerosolization of prepared dry powder. The ivermectin dry powder was prepared with a mini spray-dryer (Buchi B-290), using a 23 factorial design and manipulating spray-drying conditions such as feed concentration (0.2% w/v and 0.8% w/v), inlet temperature (80 °C and 100 °C) and presence/absence of L-leucine (0% and 10%). The prepared dry powder was in the size range of 1–5 μm and amorphous in nature with wrinkle morphology. We observed a higher fine particle fraction (82.5 ± 1.4%) in high feed concentration (0.8% w/v), high inlet temperature (100 °C) and the presence of L-leucine (10% w/w). The stability study conducted for 28 days confirmed that the spray-dried powder was stable at 25 ± 2 °C/<15% RH and 25 ± 2 °C/ 53% RH. Interestingly, the ivermectin dry powder formulation inhibited SARS-CoV-2 replication in vitro with a potency similar to ivermectin solution (EC50 values of 15.8 µM and 14.1 µM, respectively), with a comparable cell toxicity profile in Calu-3 cells. In summary, we were able to manipulate the spray-drying conditions to develop an effective ivermectin inhalable dry powder. Ongoing studies based on this system will allow the development of novel formulations based on single or combinations of drugs that could be used to inhibit SARS-CoV-2 replication in the respiratory tract.

Spray-Dried Griseofulvin-Lactose Matrix for Enhanced Solubility Using a Spray-Drying Biochemical Process

Griseofulvin (GF) is a hydrophobic drug with a low solubility. In order to improve the solubility of GF, which has low water solubility, this report uses the spray-drying technique to prepare complexes with lactose to promote the solubility and oral bioavailability of GF. The solution samples were spray dried using different ratios of ethanol or acetone solutions as dissolution media. By characterization of the obtained spray-dried powders, we found that the solubility of the different groups of samples obtained by spray drying was increased, and similarly, their dissolution rates were also increased to different degrees. By comparison, the greatest increase in solubility was obtained in an aqueous acetone solution, showing the greatest ability and efficiency of acetone in promoting the solubility of GF during the spray-drying process.

Drug Product Characterization of High Concentration Non-Aqueous Protein Powder Suspensions

High concentration protein formulations for subcutaneous injection represent a substantial number of development projects in the pharmaceutical industry. Such concentrated aqueous protein solutions face some specific challenges such as increased viscosity and aggregation propensity. Protein powder suspensions in non-aqueous vehicles could be an alternative providing lower viscosity than the respective aqueous solution. The choice of potential suspension vehicles is limited as traditional non-aqueous liquids, such as oils, show an inherent high viscosity. We studied suspensions prepared by dispersing spray-dried protein powder in different vehicles including sesame oil and medium chain triglycerides, as well as fluorinated and semifluorinated alkanes. We found, that semifluorinated alkanes enable formulations with high concentrations up to 280 mg/ml monoclonal antibody with a low viscosity of less than 10 mPa·s and low injection forces. The glide force of suspensions containing 210 mg/ml protein was not affected by the particle size of the spray-dried powders with medians ranging from 1 to 14 µm. In contrast, suspensions prepared with cryo-milled powder showed markedly higher viscosities and were not injectable at the same concentration. Protein powder suspensions were syringeable using a 25G needle. Vial filling using a peristaltic pump was possible and lead to a uniform filling. Sedimentation of the suspension was slow and does not lead to challenges upon vial filling during manufacturing or transfer of the suspension into syringes. Thus, we could show that dispersions of spray-dried protein powders in non-aqueous vehicles, such as semifluorinated alkanes, are a promising alternative to aqueous protein solutions at high concentrations.

Polymeric Microparticles: Synthesis, Characterization and In Vitro Evaluation for Pulmonary Delivery of Rifampicin.

Rifampicin, a potent broad-spectrum antibiotic, remains the backbone of anti-tubercular therapy. However, it can cause severe hepatotoxicity when given orally. To overcome the limitations of the current oral therapy, this study designed inhalable spray-dried, rifampicin-loaded microparticles using aloe vera powder as an immune modulator, with varying concentrations of alginate and L-leucine. The microparticles were assessed for their physicochemical properties, in vitro drug release and aerodynamic behavior. The spray-dried powders were 2 to 4 µm in size with a percentage yield of 45 to 65%. The particles were nearly spherical with the tendency of agglomeration as depicted from Carr’s index (37 to 65) and Hausner’s ratios (>1.50). The drug content ranged from 0.24 to 0.39 mg/mg, with an association efficiency of 39.28 to 96.15%. The dissolution data depicts that the in vitro release of rifampicin from microparticles was significantly retarded with a higher L-leucine concentration in comparison to those formulations containing a higher sodium alginate concentration due to its hydrophobic nature. The aerodynamic data depicts that 60 to 70% of the aerosol mass was emitted from an inhaler with MMAD values of 1.44 to 1.60 µm and FPF of 43.22 to 55.70%. The higher FPF values with retarded in vitro release could allow sufficient time for the phagocytosis of synthesized microparticles by alveolar macrophages, thereby leading to the eradication of M. tuberculosis from these cells.