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.
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