Pengembangan Mikrosfer Asiklovir menggunakan Kitosan dan Natrium Tripolifosfat: Faktor Suhu Inlet

Abstract—Acyclovir is an antiviral used for the treatment of herpes simplex but it's a short half-life, thereby increasing the administration frequency. To overcome this problem, the acyclovir microsphere system was created with chitosan and sodium tripolyphosphate (NTPP). The formulation used a spray drying method which is influenced by the inlet temperature. Three variations of the inlet temperature are given, i.e. 170 oC (M1), 180 oC (M2), and 190 oC (M3). Physicochemical characterization obtained the same results on the three microspheres. They showed the occurrence of cross-linking between chitosan and NTPP. The average particle sizes of M1, M2, and M3 microspheres were 8.52 µm, 8.92 µm, and 9.83 µm respectively. All microspheres' morphology was spherical with a rough surface. The moisture content of M1, M2, M3 microspheres were 6.63%, 5.49%, 4.63%, respectively. The swelling index of M1, M2, and M3 microspheres obtained from 0.5-4 hours were 143.11-258.86%, 167.26-239.61%, and 152.49-259.60%. The recovery of M1, M2, and M3 microspheres was 33.93%, 47.26%, and 35.09% respectively. The acyclovir encapsulation efficiency of M1, M2, and M3 microspheres were 115.32%, 117.14%, and 111.16% respectively. Dissolution testing showed all three microspheres have the potential for controlled drug delivery systems. The inlet temperature affects the microsphere characteristics and the best inlet temperature was 180 oC.   Abstrak—Asiklovir merupakan antivirus yang digunakan untuk terapi herpes simplex karena tingkat selektivitasnya tinggi tetapi waktu paruhnya cepat sehingga meningkatkan frekuensi pemberiannya. Untuk mengatasi masalah ini asiklovir dibuat sistem mikrosfer. Dalam penelitian ini kitosan digunakan sebagai polimer dan natrium tripolifosfat (NTPP) sebagai penyambung silang. Pembuatannya menggunakan metode spray drying yang dipengaruhi oleh suhu inlet, sehingga diberikan tiga variasi suhu inlet yaitu 170 oC (M1), 180 oC (M2), dan 190 oC (M3). Karakteristisasi fisikokimia meliputi identifikasi gugus fungsi, perubahan melting point, dan energi entalpi memperoleh hasil yang sama pada ketiga mikrosfer yaitu terjadinya ikatan sambung silang antara kitosan dengan NTPP. Ukuran partikel rata-rata mikrosfer M1, M2, M3 berturut-turut adalah 8,52 µm, 8,92 µm dan 9,83 µm. Morfologi bentuk ketiga mikrosfer adalah sferis dengan permukaan kasar. Kandungan lembap mikrosfer M1, M2, M3 berturut-turut adalah 6,63%, 5,49%, 4,63%. Indeks pembengkakan mikrosfer M1, M2, M3 yang diperoleh dari 0,5-4 jam berturut-turut adalah 143,11-258,86%, 167,26-239,61% dan 152,49-259,60%. Perolehan kembali mikrosfer M1, M2, M3 berturut-turut adalah 33,93%, 47,26% dan 35,09%. Efisiensi enkapsulasi asiklovir M1, M2, M3 berturut-turut adalah 115,32%, 117,14% dan 111,16%. Pengujian disolusi asiklovir menunjukkan ketiga mikrosfer berpotensi untuk sistem penghantaran obat terkendali. Suhu inlet berpengaruh terhadap karakteristik mikrosfer asiklovir dan suhu terbaik adalah 180 oC

Pengembangan Mikrosfer Asiklovir menggunakan Kitosan dan Natrium Tripolifosfat: Faktor Suhu Inlet

Abstract—Acyclovir is an antiviral used for the treatment of herpes simplex but it's a short half-life, thereby increasing the administration frequency. To overcome this problem, the acyclovir microsphere system was created with chitosan and sodium tripolyphosphate (NTPP). The formulation used a spray drying method which is influenced by the inlet temperature. Three variations of the inlet temperature are given, i.e. 170 oC (M1), 180 oC (M2), and 190 oC (M3). Physicochemical characterization obtained the same results on the three microspheres. They showed the occurrence of cross-linking between chitosan and NTPP. The average particle sizes of M1, M2, and M3 microspheres were 8.52 µm, 8.92 µm, and 9.83 µm respectively. All microspheres' morphology was spherical with a rough surface. The moisture content of M1, M2, M3 microspheres were 6.63%, 5.49%, 4.63%, respectively. The swelling index of M1, M2, and M3 microspheres obtained from 0.5-4 hours were 143.11-258.86%, 167.26-239.61%, and 152.49-259.60%. The recovery of M1, M2, and M3 microspheres was 33.93%, 47.26%, and 35.09% respectively. The acyclovir encapsulation efficiency of M1, M2, and M3 microspheres were 115.32%, 117.14%, and 111.16% respectively. Dissolution testing showed all three microspheres have the potential for controlled drug delivery systems. The inlet temperature affects the microsphere characteristics and the best inlet temperature was 180 oC.   Abstrak—Asiklovir merupakan antivirus yang digunakan untuk terapi herpes simplex karena tingkat selektivitasnya tinggi tetapi waktu paruhnya cepat sehingga meningkatkan frekuensi pemberiannya. Untuk mengatasi masalah ini asiklovir dibuat sistem mikrosfer. Dalam penelitian ini kitosan digunakan sebagai polimer dan natrium tripolifosfat (NTPP) sebagai penyambung silang. Pembuatannya menggunakan metode spray drying yang dipengaruhi oleh suhu inlet, sehingga diberikan tiga variasi suhu inlet yaitu 170 oC (M1), 180 oC (M2), dan 190 oC (M3). Karakteristisasi fisikokimia meliputi identifikasi gugus fungsi, perubahan melting point, dan energi entalpi memperoleh hasil yang sama pada ketiga mikrosfer yaitu terjadinya ikatan sambung silang antara kitosan dengan NTPP. Ukuran partikel rata-rata mikrosfer M1, M2, M3 berturut-turut adalah 8,52 µm, 8,92 µm dan 9,83 µm. Morfologi bentuk ketiga mikrosfer adalah sferis dengan permukaan kasar. Kandungan lembap mikrosfer M1, M2, M3 berturut-turut adalah 6,63%, 5,49%, 4,63%. Indeks pembengkakan mikrosfer M1, M2, M3 yang diperoleh dari 0,5-4 jam berturut-turut adalah 143,11-258,86%, 167,26-239,61% dan 152,49-259,60%. Perolehan kembali mikrosfer M1, M2, M3 berturut-turut adalah 33,93%, 47,26% dan 35,09%. Efisiensi enkapsulasi asiklovir M1, M2, M3 berturut-turut adalah 115,32%, 117,14% dan 111,16%. Pengujian disolusi asiklovir menunjukkan ketiga mikrosfer berpotensi untuk sistem penghantaran obat terkendali. Suhu inlet berpengaruh terhadap karakteristik mikrosfer asiklovir dan suhu terbaik adalah 180 oC

PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTES OF TREHALOSE AND INULIN AS STABILIZER

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and the optimal ratio of trehalose and inulin as critical material attributes (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method. Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula. Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5%, and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively. Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no delay in the SFD process and when the FD is in operation, it should not be interrupted until the powder is dry. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1

The Effect of Chitosan Concentration Cross-Linking with Sodium Tripolyphosphate on Acyclovir Spray Dried Microspheres

Acyclovir is an antiviral drug with poor absorption and short half-time elimination. This problem can be solved by delivery system modification with microspheres prepared by spray drying method using chitosan crosslinking with sodium tripolyphosphate (STTP). This study observe the effect of different chitosan concentration, 0,5% chitosan (S1), 0,75% chitosan (S2), and 1% chitosan (S3) on the microspheres’s physico-chemical characteristics. Microspheres were characterized for functional groups identification and change in melting point and enthalpy energy using FTIR and DSC, particle size, surface morphology, yield, encapsulation efficiency, moisture content, swelling behavior, and in vitro drug release. Decriptively, functional groups identification and change in melting point and enthalpy energy of S1, S2, and S3 microspheres showed that acyclovir has been encapsulated by cross-linked matrix of chitosan-STPP. Surface morphology of particles revealed that S1 and S2 microspheres have non spherical form with rough surface, while S3 have smoother surface. The result showed that chitosan concentration affect the particle size (1-19 µm), yield and moisture content of microspheres. Swelling index and in vitro drug release study revealed that higher chitosan concentration showed a significant decrease of two parameters, with sustained relase behavior. In conclusion, all three formula are potential for controlled drug release and S3 is the best microspheres

VALIDASI PROSES PEMBUATAN DAN PENETRASI PATCH TIPE MATRIKS NATRIUM DIKLOFENAK

The aim of this study was to prove that the penetration test of diclofenac sodium matrix type transdermal patch fulfilled the acceptance criteria of formulation process validation (coefficient of variance (CV) of diclofenac sodium penetration f1ux). Diclofenacsodiummatrix type transdermal patch was prepared by mixing of ethyl cellulose and polyvinylpyrrolidone aspolymer base, polyethylene glycol 400 as plasticizer and mixing of diclofenac sodium as active ingredientto menthol solution as enhancer. The first composition of patch was contained ratio polymer ethyl cellulose and polyvinylpyrrolidone of 7:3 (Formula I) and the second composition of patch was contained ratio polymer ethyl cellulose and polyvinylpyrrolidone of 6:4 (Formula II). The evaluation included physical characteristics of patch(organoleprics, moisture content, surface homogenity using Scanning Electron Microscope (SEM), drug content and content uniformity) and penetration test.The penetration of diclofenac sodium through Wistar rat skin membrane was determined by dissolution test, which was carried out using apparatus type 5-paddle overdisk in phosphate buffer pH 7.4 (37±0.5'C, 50 rpm). The process validation was carried out for 3 days, with 3 times replication. From the results of penetration tests showed CV of diclofenac sodium penetration f1ux<6% (both of Formula I and Formula II) and one-way ANOVA analysis showed no significant difference of sodium diclofepac patch (p=0,745 for formula I and p=0,315 for formula II) were performed on 3 different days. This study revealed that penetration test of two formulas diclofenac sodium matrix type transdermal patch fulfilled the acceptance criteria of formulation process validatio

Effect Of Carbomer 940 Concentration to Physics And pH Characteristics Of Aloe Vera Soothing Gel

Soothing gel is a multi-purpose gel which can be used for many purposes include prevention of dry skin. This research aims to investigate the change of the physics characteristics and pH of Aloe vera soothing gel. Concentration ratio of carbomer 940 as gelling agent and triethanolamine as the basis gel is 1:1. This research compares three different formulas that contain different variation of carbomer concentration which were formula I with 0.6% concentration, formula II with 0.8% concentration, and formula III with 1% concentration. The parameters of physics characteristics and pH were observed. The parameters are organoleptis, viscosity, flow characteristics, dispersive capability, density, and pH. The research is conducted in three replication in each formula. The result shows that all formulas fulfilled all specifications. The carbomer concentration affect the physical parameter characteristic of the soothing gel, but it did not affect the pH of soothing gel. Formula I is the best formula based on soothing gel specification

Stability study of spray freeze-dried insulin dry powder formulations used for nose-to-brain delivery

Insulin is classified as a cold chain product due to being a peptide hormone with stability issues in the liquid preparation. Therefore, insulin was developed into the dry powder form to improve the stability and application for nose-to-brain delivery in Alzheimer’s disease treatment. Insulin was physically engineered through the addition of sugar stabilizers with seven different weight ratios of trehalose to inulin, labeled as F1–F7, and prepared using the spray freeze-drying (SFD) method. The obtained SFD insulin dry powders (IDP) were characterized physically and chemically. In addition, the long-term stability study was conducted at 25°C and 40°C for 6 months, whereas the accelerated stability study was examined at 40°C, 50°C, and 60°C for 1 month. This study aims to obtain the most stable IDP formulation. The results show that IDP F3, composed of trehalose and inulin 1:1 w/w, was the superior formula. Moreover, IDP F3 exhibited spherical shapes with rough surfaces, amorphous crystallinity, and high insulin content of 100%. Furthermore, IDP F3 indicated the proper stability for 6 months, including insulin content, transition glass temperature (Tg), and moisture content. According to stability study results, the k25 value, half-life, and shelf life of IDP F3 were (1.77 ± 0.06)×10−2 week−1, 39.17 ± 1.34 weeks, and 5.93 ± 0.20 weeks, respectively

Promising brain biodistribution of insulin via intranasal dry powder for nose-to-brain delivery

Nose-to-brain delivery (NTBD) offering potential benefits for treating Alzheimer’s disease. In previous research, insulin dry powder (IDP) formulation for NTBD was developed, exhibiting favorable stability. This study aims to conduct in vitro and ex vivo assessment of release, permeation, mucoadhesion and histopathology, as well as an in vivo biodistribution study to produce IDP for NTBD and evaluate brain biodistribution. Spray-freeze-dried IDP formulations with varying weight ratios of trehalose-to-inulin were produced and analyzed. The release study was carried out in PBS with a pH of 5.8 stirred at 50 rpm and maintained at 37 ◦C ± 0.5 ◦C. Goat nasal mucosa was used for ex vivo permeation and mucoadhesion testing under similar conditions. An ex vivo histopathological examination and an in vivo study using enzyme-linked immunosorbent assay, were also performed. The IDP dissolution study demonstrated complete release of all IDPs within 120 min. The permeation study indicated that steady-state conditions were observed between 30 and 240 min. The mucoadhesion study unveiled that IDP F5 exhibited the fastest mucoadhesion time and the least force required within the fastest time of 43.60 ± 2.57 s. The histopathological study confirmed that none of the tested IDPs induced irritation in the nasal mucosa. Furthermore, the biodistribution study demonstrated the absence of detectable insulin in the plasma, while IDP F3 exhibited the highest deposited concentration of insulin within both the olfactory bulb and the whole brain. The extensive evaluation of the IDP formulations through in vitro, ex vivo, and in vivo studies implies their strength non-invasive NTBD. IDP F3, with a 1:1 wt ratio of trehalose to inulin, exhibited favorable brain biodistribution outcomes and was recommended for further investigation and development in the context of NTBD

Effect of lung function disorders and physical activity on smoking and non-smoking students

Background. The number of young smokers is increasing, and hence their risk of respiratory problems. This risk is exacerbated by their low level of physical activity, which also reduces lung function. This study aimed to determine differences in lung function and levels of physical activity between smokers and non-smokers. Method. This research was conducted from October 2019 to January 2020. The research design was cross-sectional, and a purposive sampling method was used. Pulmonary function was measured by means of spirometry, while physical activity was measured through a modified International Physical Activity Questionnaire (IPAQ). Results. We enrolled 124 university students: 62 smokers and 62 non-smokers. A significant difference in lung function values (< 70 vs ≥ 70) was observed between smokers and non-smokers (p = 0.00). No difference (p = 0.907) in the level of physical activity was seen between smokers and non-smokers, with most subjects in both groups displaying moderate levels. Conclusions. Students who smoked had more respiratory problems than those who did not. Although the level of physical activity did not correlate with respiratory problems, these problems were more common in the vigorous catgory

Utilization of Green Tea Extract on Anti-aging Cream with Butylated Hydroxytoluene (BHT) and Tertiary Butylhydroquinone (TBHQ): Physical Stability Aspect

Green tea (Camellia sinensis (L.) Kuntze) is a potent natural ingredient with flavonoid content that can be used as an antioxidant and anti-aging for skincare products. The formula containing green tea extract is usually formulated as oil in water emulsion or cream. The active components of green tea are catechins which are characterized as less stable against oxidation. Therefore, it is needed to add other antioxidants such as ButylatedHydroxy Toluene (BHT) and Tertiary–Butyl Hydroquinone (TBHQ) to protect the product from degradation. The aim of this study was to obtain a physically stable antiaging cream formula. Each formula was tested for physical stability by measuring several variables including organoleptic, pH, relative density, viscosity, and flow properties, as well as droplet size. Accelerated stability testing is carried out for 3 mo at 40 °C and 75 % relative humidity. The results found that cream with the BHT formula is more stable than the TBHQ formula in terms of the parameters of density and droplet size. While the TBHQ formula only gave better stability in pH, the other variables from both formulas remain stable in 3 mo. It can be concluded that the green tea extract cream with BHT antioxidant is more stable than the TBHQ