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Abstrak :
Tuberkulosis adalah penyakit yang disebabkan oleh Mycobacterium tuberculosis dan merupakan suatu penyakit global yang menjadi perhatian di dunia karena kemudahan transmisi ke orang lain. Isoniazid merupakan salah satu OAT lini pertama yang menjadi dasar obat tuberculosis dan terjadinya resistensi terhadap isoniazid menjadi salah satu kendala pemberantasan TB di Indonesia. Tuberkulosis ekstrapulmonal merupakan suatu komplikasi dari Mycobacterium tuberculosis di luar dari paru. Tuberkulosis ekstrapulmonal memiliki angka insidensi yang cukup tinggi dalam kejadian tuberkulosis. Diagnosis tuberkulosis ekstrapulmonal ditegakkan dengan pemeriksaan BTA dari isolat ekstrapulmonal seperti pus dan cairan sendi. Penelitian ini bertujuan menentukan pola resistensi M. tuberculosis terhadap isoniazid serta mengetahui perbandingan angka kejadian resistensi pada spesimen pus dan spesimen sputum. Penelitian ini dilakukan dengan menganalisis data sekunder sebanyak 676 sampel dengan kultur positif dari Departemen Mikrobiologi FKUI pada September 2005 sampai Desember 2007 dan telah menjalani pemeriksaan resistensi sesuai dengan panduan WHO/IUATLD. Dari hasil analisis didapatkan bahwa pola resistensi terhadap isoniazid sebanyak 13.5%. dan terdapat perbedaan angka resistensi sebesar 19.49 %, di mana spesimen pus lebih tinggi.

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Tuberculosis is a disease caused by Mycobacterium tuberculosis and becomes very dangerous because its transmission potency to infect other people. Isoniazid is one of the first line tuberculosis? drugs and its resistance will be the obstacle of reducing Tuberculosis cases in Indonesia. Extrapulmonary tuberculosis is one of complication from Mycobacterium tuberculosis in everywhere instead of lung. Extrapulmonary tuberculosis has quite high incidence rate in tuberculosis case. Diagnosis of extrapulmonary tuberculosis is decided by BTA test from extrapulmonal isolate such as pus and synovial liquid. This research aimed to determine the resistance of isoniazid and also determine the ratio of resistant in pus specimen and sputum specimen. This research was done by collecting and analyzing 676 secondary samples which culture results are positive from Microbiology Department Medical Faculty University of Indonesia in September 2005 until December 2007 and had undergone resistance tests based on WHO/IUATLD guidelines. The results of the analysis was obtained that resistance of isoniazid was 13.5%. and there are 19.49 % difference of resistance, where pus specimen is higher.

Abstrak :
Jalur metabolisme utama dari isoniazid INH adalah dengan asetilasi untuk membentuk asetil isoniazid AcINH . Kecepatan asetilasi dapat berbeda tergantung aktivitas N-asetiltransferase-2 NAT-2 . Pengobatan tuberkulosis dengan INH dapat menimbulkan risiko hepatotoksik, baik pada tipe asetilator cepat maupun lambat. Buah nans Ananas comosus Linn. Merr diketahui beraktivitas hepatoprotektor. Tujuan penelitian adalah untuk mempelajari kecepatan asetilasi INH pada etnis Melanesia dari Papua. Selain itu, penelitian bertujuan untuk mengetahui pengaruh jus nanas terhadap asetilasi INH. Kecepatan asetilasi INH ditentukan berdasarkan rasio kadar AcINH dan INH dalam plasma subjek. Kadar AcINH dan INH dalam plasm asubjek dianalisis dengan kromatografi cair kinerja tinggi. Kromatografi fase balik-pasngan ion yang telah divalidasi menunjukkan batas kuntifikasi terendah untuk INH dan AcINH berturut-turut yaitu 0,1258 dan 0,1188ug/mL. Subjek yang berpartisipasi pada studi penentuan asetilasi INH adalah 102 orang. Sebanyak 41 dari 102 subjek secara sukarela terlibat pada studi pengaruh jus buah nanas pada asetilasi INH. Hasil penelitian menunjukkan 70,59 subjek adalah asetilator lambat. Jus buah nanas matang diketahui memengaruhi kecepatan asetilasi INH berdasarkan analisis statistik Wilcoxon test for two related samples pada tingkat kepercayaan 95 . Dalam rangka mengurangi efek hepatotoksik INH, pemanfaatan jus nanas matang sebagai adjuvant dapat diteliti lebih lanjut pada pasien tuberkulosis.

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The major pathway of INH metabolism is by acetylation to form acetyl isoniazid AcINH . Acetylation rate may differ depends on N acetyltransferase 2 NAT 2 activity. Treatment of tuberculosis with INH may lead to the risk of hepatotoxicity, both in fast and slow acetylator types. Pineapple fruit Ananas comosus Linn. Merr has a hepatoprotector activity. The aim of this study was to study INH acetylation rate on Melanesia ethnicity from Papua, Indonesia. Furthermore, this study was to evaluate the influence of pineapple juice as hepatoprotector in INH acetylation. The acetylated rate of INH was determined based on the ratio of AcINH and INH levels in subject rsquo s plasma. The levels of INH and AcINH in the subject rsquo s plasma were analyzed by high performance liquid chromatography. Validated reversed phase ion pair chromatography showed the lower limit of quantification of INH and AcINH were 0.1258 and 0.1188 g mL, respectively. Participants in the study of INH acetylator status were 102 subjects. A total of 41 of 102 subjects were voluntarily implicated in the study of the effect of pineapple juice on acetylation of INH. The results showed that 70.59 of subjects were slow acetylators. Ripe pineapple fruit juice is known to affect the rate of acetylation INH based on statistical analysis of Wilcoxon test for two related samples at 95 confidence level. In order to reduce the effects of INH hepatotoxicity, the utilization of ripe pineapple juice as adjuvant can be further investigated in patients with tuberculosis.

Abstrak :
Rifampisin dan isoniazid merupakan regimen pengobatan tuberkulosis utama yang memerlukan pengukuran kadar dalam darah untuk mengoptimalkan proses pengobatan dan mencegah resistensi. Metode biosampling yang sering digunakan memiliki keterbatasan terkait kenyamanan pasien. Volumetric Absorptive Microsampling (VAMS) hadir untuk mengatasi keterbatasan tersebut. Penelitian ini bertujuan untuk mengembangkan dan mengaplikasikan teknik biosampling VAMS untuk analisis rifampisin dan isoniazid pasien tuberkulosis menggunakan kromatografi cair kinerja tinggi-photodiode array. Sampel VAMS diekstraksi menggunakan 1 mL asetonitril dengan baku dalam cilostazol dan dianalisis menggunakan kromatografi cair kinerja tinggi pada suhu kolom 40°C yang terdeteksi pada 261 nm. Fase gerak yang digunakan terdiri dari 50mM buffer amonium asetat pH 5,0-asetonitril-metanol (40:30:30) dengan laju alir 0,5 mL/menit selama 15 menit. Metode ini telah memenuhi persyaratan parameter validasi yang ditetapkan oleh FDA tahun 2018 yaitu selektivitas, carry-over, batas bawah kuantifikasi, linearitas, akurasi, presisi, perolehan kembali, integritas pengenceran, dan stabilitas. Analisis dilakukan dengan kurva kalibrasi pada kisaran 1,0–30 μg/ml untuk rifampisin dan 0,4-20 μg/ml untuk isoniazid. Hasil analisis dari 21 pasien tuberkulosis RSUD dr. Chascullah Abdulmadjid Kota Bekasi menunjukkan bahwa 52,38% pasien memiliki konsentrasi darah yang rendah pada setidaknya salah satu obat, 28,57% pasien berada dalam kisaran terapeutik, dan 23,81% memiliki konsentrasi isoniazid yang tinggi dalam darah. Penyesuaian dosis diperlukan untuk sebagian besar pasien yang memiliki konsentrasi subterapetik. Metode ini efektif untuk mendukung pemantauan terapi rifampisin dan isoniazid terkait kenyamanan dan keamanan pasien. ......Rifampicin and isoniazid are anti-tuberculosis drugs that require measurement of blood levels to optimize the treatment process and prevent resistance. The conventional biosampling technique often used has limitations related to patient comfort. Volumetric Absorptive Microsampling (VAMS) exists to overcome it. This study aims to develop and apply the VAMS technique for the analysis of rifampicin and isoniazid in tuberculosis patients using a high-performance liquid chromatography-photodiode array. VAMS samples were extracted using 1 mL of acetonitrile with internal standard cilostazol and analyzed using high-performance liquid chromatography at a column temperature of 40°C detected at 261 nm. The mobile phase used consisted of 50 mM ammonium acetate buffer pH 5.0, acetonitrile, and methanol (40:30:30) with a flow rate of 0.5 mL/minute for 15 minutes. This method has met the validation parameter requirements set by the FDA in 2018, namely selectivity, carry-over, lower limit of quantification, linearity, accuracy, precision, recovery, dilution integrity, and stability. Analysis was carried out with a calibration curve in the range of 1.0–30 μg/ml for rifampicin and 0.4–20 μg/ml for isoniazid. The results from 21 tuberculosis patients of RSUD Dr. Chascullah Abdulmadjid Bekasi showed that 52.38% of patients had low blood concentrations of at least one of the drugs, 28.57% of patients were in the therapeutic range, and 23.81% had high concentrations of isoniazid. Dosage adjustments are necessary for most patients who have subtherapeutic concentrations. This method is effective in supporting the monitoring of rifampicin and isoniazid therapy regarding patient comfort and safety.

Abstrak :
Isoniazid merupakan lini pertama dalam terapi TB bersama dengan rifampisin, pirazinamid, dan etambutol (Vilcheze & Jacobs, 2019). Isoniazid merupakan salah satu obat lini pertama yang penting karena memiliki aktifitas bakterisidal awalnya yang kuat. Resistensi terhadap isoniazid diketahui dapat menurunkan keberhasilan terapi TB dan meningkatkan risiko munculnya resistensi terhadap obat lini pertama lainnya seperti rifampisin (Byung & Won, 2019. Tugas ini bertujuan untuk melakukan pengkajian resep terhadap pengobatan TB dengan obat utama Isoniazid di Apotek Roxy Pondok Labu sehingga dapat melihat kerasionalan resep sehingga mencegah terjadinya ketidaktepatan penggunaan obat-obatan TB yang dapat mempengaruhi keberhasilan terapi dan munculnya resistensi obat. Pengkajian resep diawali dengan pemilihan resep yang dilayani oleh Apotek Roxy periode 1-31 Maret 2021. Pengkajian dilakukan terhadap aspek administratif, farmasetik, dan klinis. Hasil pengkajian secara umum sudah sesuai dan lengkap, serta disimpulkan bahwa pasien diduga mengalami tuberkulosis resisten-rifampisin sehingga diberikan kombinasi antibiotik isoniazid, ofloksasin, dan etambutol. ......Isoniazid is the first line of TB therapy together with rifampin, pyrazinamide, and ethambutol (Vilcheze & Jacobs, 2019). Isoniazid is one of the most important first-line drugs because of its strong initial bactericidal activity. Resistance to isoniazid is known to reduce the success of TB therapy and increase the risk of developing resistance to other first-line drugs such as rifampin (Byung & Won, 2019. This task aims to evaluate prescriptions for TB treatment with the primary drug Isoniazid at Apotek Roxy Pondok Labu to see the rationale for medications to prevent inaccuracies in the use of TB drugs which can affect the success of therapy and the emergence of drug resistance. The evaluation begins with the selection of prescriptions served by the Apotek Roxy for the period 1-31 March 2021. The assessment is carried out on administrative, pharmaceutical, and clinical aspects. The evaluation results were generally appropriate and complete, and it was concluded that the patient was suspected of having rifampin-resistant tuberculosis and was therefore given a combination of isoniazid, ofloxacin, and ethambutol antibiotics.

Abstrak :
Pendahuluan: Kadar obat yang rendah dalam darah pasien TB paru diduga berhubungan dengan respon pengobatan yang buruk seperti kegagalan konversi sputum mikroskopis, yang merupakan risiko terjadinya kegagalan pengobatan. Namun berbagai penelitian menunjukan hasil kontroversial, sebagian menunjukan terdapat hubungan antara kadar obat dengan konversi sputum akhir intensif, sebagian lagi menunjukan respon terapi yang sama baiknya untuk kadar normal maupun kadar rendah. Faktor yang diduga menyebabkan perbedaan hasil ini adalah perbedaan MIC rifampisin dan isoniazid terhadap Mycobacterium tuberculosis (MTB) pada pasien-pasien TB di setiap wilayah. Penelitian ini bertujuan mengetahui hubungan kadar rifampisin dan isoniazid darah dengan konversi, serta hubungan rasio kadar puncak rifampisin dan isoniazid darah terhadap MIC (Cmax/MIC) dengan konversi sputum pasien TB paru di akhir fase intensif. Metode: Desain penelitian adalah kasus kontrol dengan jumlah sampel sebanyak 40 orang, yang terbagi dalam kelompok kasus (tidak konversi, n=20) dan kelompok kontrol (konversi, n=20). Kadar rifampisin dan isoniazid darah diukur pada dua jam setelah minum obat yang merupakan perkiraan kadar puncak rifampisin dan isoniazid, menggunakan metode LC/MS-MS. Data MIC diambil dari 20 isolat kultur MTB sputum pasien TB paru kasus baru di RSP dr. H.A Rotinsulu Bandung menggunakan metode MGIT. Hasil: Dari 40 pasien didapatkan rerata kadar rifampisin 5,58±2,41 mg/L dengan 36 pasien (90%) diantaranya memiliki kadar puncak di bawah normal. Untuk isoniazid didapatkan median kadar 1,46 (0,40-6,10) mg/L dengan 32 pasien (80%) diantaranya memiliki kadar puncak isoniazid di bawah normal. Pada penelitian ini didapatkan MIC rifampisin 0,25 mg/L dan MIC isoniazid 0,05 mg/L, lebih rendah dibanding kadar kritis masing-masing obat. ......Introduction: Low plasma drug concentration in pulmonary TB patients are thought to be associated with poor treatment outcomes such as microscopic sputum conversion failure, which is a risk of treatment failure. However, various studies showed controversial results, some showed that there was an association between drug concentration with sputum conversion at the end of intensive phase, while others showed the same good outcome for normal and low concentrations. Factors thought to cause these controversial in results are the differences in the MIC of rifampicin and isoniazid against Mycobacterium tuberculosis in TB patients in each region. This study aims to determine the association between blood rifampicin and isoniazid concentratiom with sputum conversion, as well as the association between the ratio of peak blood concentration of rifampicin and isoniazid to MIC (Cmax/MIC) with sputum conversion of pulmonary TB patients at the end of the intensive phase. Methods: The study design was a case-control study with a sample size of 40 subjects, which were divided into a case group (non-conversion, n=20) and a control group (conversion, n=20). The blood concentration of rifampicin and isoniazid were measured two hours after taking the drug which is an estimate of the peak concentrations of rifampicin and isoniazid, using the LC/MS-MS method. MIC data were taken from 20 MTB sputum culture isolates from new cases of pulmonary TB patients at RSP dr. H.A Rotinsulu Bandung using the MGIT method. Results: Of the 40 patients, the mean concentration of rifampicin was 5.58 ± 2.41 mg/L with 36 patients (90%) of whom had peak concentrations below normal. For isoniazid, the median concentration was 1.46 (0.40-6.10) mg/L with 32 patients (80%) of whom had peak concentration of isoniazid below normal. In this study, the MIC of rifampicin 0.25 mg/L and MIC of isoniazid 0.05 mg/L were lower than the critical concentration of each drug. There was no association between blood rifampicin concentration (OR: 11.18; 95% CI: 0.20-223.00, p= 0.106), blood isoniazid concentration (OR: 3.86; 95% CI: 0.67-22 .22, p= 0.235), and the Cmax/MIC ratio of rifampicin (OR: 0.474; 95% CI: 0.039-5.688, p=1.00) with intensive final sputum conversion. However, there was an association between low concentration of both drugs simultaneously (OR: 6.00; 95% CI: 1.08-33.27, p = 0.028), and the Cmax/MIC ratio of isoniazid (OR: 4.333; 95% CI: 1.150). -16,323, p= 0.027) with sputum conversion at the end of the intensive phase. Conclusion: There was no association between blood rifampicin concentration, blood isoniazid concentration, and the Cmax/MIC ratio of rifampicin with microscopic sputum conversion at the end of the intensive phase. However, there was an association between low concentration of both drugs and the Cmax/MIC ratio of isoniazid and sputum conversion at the end of the intensive phase.

Abstrak :
Tuberkulosis (TBC) masih menjadi penyebab utama kematian akibat penyakit menular oleh adanya infeksi. Rifampisin dan isoniazid adalah obat lini pertama yang paling efektif melawan infeksi Mycobacterium tuberculosis. Deteksi resistansi OAT yang tepat, akurat, dan komprehensif, serta pemilihan sampel diperlukan untuk memastikan diagnosis penyakit tuberkulosis pasien. Penelitian ini bertujuan untuk menganalisis perbandingan hasil targeted drug sequencing dari hasil dekontaminasi sputum dengan isolat Mycobacterium tuberculosis dan mengetahui kesesuaian DST fenotipik MGIT, genotipik GeneXpert dalam mendeteksi resistansi rifampisin dan isoniazid. Sampel penelitian ini adalah sampel sputum yang sudah ada hasil GeneXpert positif dan isolate kultur dengan hasil DST MGIT. Hasil dekontaminasi sputum langsung dan kultur positif dari sampel yang sama dilakukan targeted drug sequencing dengan Oxford Nanopore technology menggunakan flowcell MinION Mk1B. Hasil penelitian menunjukkan bahwa pada target gen rpoB pada 5 dari 6 sampel isolat kultur memberikan hasil gen resistan rpoB dan 1 undetermined. Pada sebagian besar dekontaminasi sputum yaitu 5 dari 6 sampel juga memberikan hasil resistan terhadap rpoB dan 1 dekontaminasi sputum yang undetermined. Hasil resistansi obat isoniazid didapatkan pada target gen inhA sebanyak 5 dari 6 isolat kultur memberikan hasil sensitif pada inhA dan 1 isolat undetermined. Sedangkan pada dekontaminasi sputum 4 dari 6 sampel memberikan hasil sensitif pada inhA dan 2 undetermined. Lalu, pada target gen katG terdapat 3 dari 6 isolat kultur memberikan hasil sensitif, 2 isolat resistan, dan 1 undetermined. Sedangkan pada dekontaminasi sputum memberikan 2 hasil sensitif, 2 hasil resistan, dan 2 hasil undetermined. Metode targeted drug sequencing dapat dilakukan dari sampel hasil dekontaminasi sputum dan isolat. Keberhasilan banyak didapatkan dari hasil kultur dibandingkan dekontaminasi sputum. Pemeriksaan dengan targeted drug sequencing memberikan hasil yang sesuai dengan hasil DST MGIT dan GeneXpert untuk deteksi gen resisten Rifampisin (rpoB) dan Isoniazid (inhA dan katG). ......Tuberculosis (TBC) is still the main cause of death due to infectious diseases. Rifampicin and isoniazid are the most effective first-line drugs against Mycobacterium tuberculosis infection. Precise, accurate and comprehensive detection of OAT resistance, as well as sample selection are needed to confirm the patient's diagnosis of tuberculosis. This study aims to compare the results of targeted drug sequencing from sputum decontamination results with Mycobacterium tuberculosis isolates and determine the suitability of MGIT phenotypic and GeneXpert genotypic DST in detecting rifampicin and isoniazid resistance. The samples for this study were sputum samples that had positive GeneXpert results and culture isolates with DST MGIT results. The results of direct sputum decontamination and positive culture from the same sample were subjected to targeted drug sequencing with Oxford Nanopore technology using a MinION Mk1B flowcell. The results showed that for the rpoB gene target, the majority of culture isolates from 5 of the 6 culture isolate samples gave rpoB resistance gene results and 1 was undetermined. In the majority of sputum decontamination, 5 out of 6 samples also gave resistance to rpoB and 1 sputum decontamination was undetermined. Isoniazid drug resistance results were obtained for the inhA gene target, 5 of the 6 culture isolates gave sensitive results for inhA and 1 isolate was undetermined. Meanwhile, in sputum decontamination, 4 of the 6 samples gave sensitive results for inhA and 2 were undetermined. Then, for the katG gene target, 3 of the 6 culture isolates gave sensitive results, 2 isolates were resistant, and 1 was undetermined. Meanwhile, sputum decontamination gave 2 sensitive results, 2 resistant results, and 2 undetermined results. The targeted drug sequencing method can be carried out from samples resulting from decontamination of sputum and isolates. Much success comes from culture results rather than sputum decontamination. Examination with targeted drug sequencing provided results that were in accordance with the results of DST MGIT and GeneXpert for the detection of Rifampicin (rpoB) and Isoniazid (inhA, and katG) resistance genes.

Abstrak :
Tuberkulosis merupakan salah satu penyebab kematian utama di dunia dan di Indonesia yang diakibatkan oleh infeksi bakteri Mycobacterium tuberculosis. Pengobatan tuberkulosis merupakan pengobatan jangka panjang dengan memberikan obat dalam bentuk kombinasi dari beberapa jenis obat antibiotik. Salah satu obat yang paling umum digunakan adalah Isoniazid. Sediaan Isoniazid yang beredar secara komersial umumnya tersedia dalam bentuk tablet. Pasien pediatri umumnya mengalami masalah dari segi farmakoterapi obat yaitu kesulitan dalam menelan obat, terutama obat sediaan padat. Peracikan obat dalam bentuk serbuk menjadi solusi utama dalam mengatasi hal tersebut, namun obat racikan serbuk menimbulkan permasalahan di praktik kefarmasian. Sediaan racikan extemporaneous dibuat untuk menggantikan obat racikan serbuk karena dinilai memiliki stabilitas yang lebih baik dan dapat menutupi rasa pahit dari obat dalam bentuk racikan serbuk sehingga cocok untuk pasien pediatri. Dalam review artikel ini akan dibahas mengenai stabilitas isoniazid dalam sediaan oral cair extemporaneous untuk pasien pediatri, dan faktor yang mempengaruhi stabilitas sediaan extemporaneous. ...... Tuberculosis is one of the major causes of death in the world and in Indonesia that comes from an infection by Mycobacterium tuberculosis. The treatment for curing Tuberculosis is a long-term treatment by giving drugs in combination of several types of antibiotic. One of the most commonly Tuberculosis drugs is Isoniazid. Isoniazid commercially available in tablet form. Some patients, especially the pediatric have problems in swallowing drugs that were formulated in solid or tablet form. Compounded drug in powder form becomes the main solution to resolve this problem, however the powder concoction drugs has some problems in pharmaceutical practice. Those problems made the pharmacists began to formulate extemporaneous preparation to replace the powder concoction because extemporaneous formulation considered to have better stability and could mask the bitter aftertaste of drugs in powder concoction, making its suitable for pediatric. This article review highlights the stability of isoniazid in extemporaneous oral liquid preparations for pediatric, also the main factors of the stability in extemporaneous preparations.

Abstrak :
Tulang belakang menjadi lokasi penyakit tuberkulosis (TB) tulang paling umum yang menyumbang sekitar setengah kasus TB tulang. Pengobatan via oral menggunakan empat obat antituberkulosis (OAT) lini pertama memiliki risiko ketidakpatuhan pasien yang tinggi dan bioavailabilitas obat di jaringan infeksi yang rendah. Penelitian terkini telah membuktikan bahwa implan tulang belakang OAT berpotensi mengatasi masalah ketidakpatuhan pasien dan meningkatkan daya jangkau obat ke daerah terinfeksi. Namun, peningkatan stres oksidatif karena respon tubuh terhadap infeksi patogen berpotensi mengakselerasi degradasi OAT isoniazid (INH) dan rifampisin (RIF). Untuk menghambat degradasi, INH dan RIF ditambahkan stabilisator dari kelas antioksidan yaitu asam galat (AG) untuk INH dan asam askorbat (AA) untuk RIF. Uji degradasi paksa dilakukan dengan terlebih dahulu membuat kurva kalibrasi obat serta menstandardisasi H2O2 stok. Sampel INH dan RIF disimpan selama 21 hari dalam media phosphate buffered saline (pH 7,4) dengan variasi konsentrasi oksidator (H2O2) dan konsentrasi stabilisator. Konsentrasi OAT diukur dengan instrumen high performance liquid chromatography (HPLC) dengan kolom C18 (250  4,6 mm  5 µm). Hasil uji degradasi menunjukkan bahwa sampel INH mengalami degradasi sebesar 82,36%, 96,55%, dan 100% akibat penambahan H2O2 0%, 0,5%, dan 1% (w/v), secara berurutan. Sementara itu, sampel INH mengalami degradasi sebesar 98,34%, 83,68%, dan 60,08% akibat penambahan AG dengan perbandingan massa INH:AG sebesar 4:1, 2:1, dan 1:1, secara berurutan. Penambahan stabilisator dengan konsentrasi yang tepat merupakan upaya untuk mengurangi oksidasi pada OAT yang diimplan di tulang belakang sehingga persamaan kinetika yang akurat dalam merepresentasikan reaksi degradasi OAT diperlukan untuk menentukan konsentrasi stabilisator yang optimal supaya menghasilkan laju degradasi OAT serendah mungkin. Model persamaan kinetika degradasi OAT menunjukkan stabilitas obat yang merupakan fungsi dari konsentrasi oksidator dan konsentrasi stabilisator. Hasil penelitian menunjukkan bahwa untuk reaksi degradasi INH dengan penambahan stabilisator AG dan kehadiran oksidator H2O2, parameter kinetika yang diperoleh yaitu k3 = 1,05 10-4 hari-1, kw = 538,95 mM, KA = 0,71 mM, dan KB = 11,01 mM-1 ......Spine is the most common site of skeletal tuberculosis (TB), which accounts for about half of skeletal TB cases. Oral treatment using four first-line antituberculosis drugs (ATD) has a high risk of patient non-adherence and low bioavailability of drugs in infected tissues. Recent research has proven that ATDs spinal implants have the potential to overcome patient non-adherence problems and it increases the drug's reach to the infected areas. However, an increase in oxidative stress due to the body's response to pathogen infection has the potential to accelerate the degradation of two ATDs, isoniazid (INH) and rifampicin (RIF). To inhibit the degradation, INH and RIF added stabilizers from the antioxidant class, namely gallic acid (GA) for INH and ascorbic acid (AA) for RIF. A forced degradation study was conducted by prior creation of calibration curves and standardization of H2O2 stock concentration. INH and RIF samples were kept for 21 days in phosphate buffered saline (pH 7,4) aqueous media with varying oxidizer concentrations (H2O2) and stabilizer concentrations. Concentration of ATDs were measured using a high performance liquid chromatography (HPLC) instrument with a C18 (250  4,6 mm  5 µm) column. The results of the degradation test showed that INH samples had a degradation of 82,36%, 96,55%, and 100% due to the addition of 0%, 0,5%, and 1% (w/v) H2O2, respectively. Meanwhile, the INH samples had a degradation of 98,34%, 83,68%, and 60,08% due to the addition of GA with a mass ratio of INH:GA of 4:1, 2:1, and 1:1, respectively. The addition of a stabilizer with the accurate concentration is an effort to reduce oxidation in ATDs implanted in the spine so that an accurate kinetic equation in representing the ATDs degradation reaction is needed to determine the optimum stabilizer concentration to produce the lowest possible ATDs degradation rate. The kinetic equation model of ATDs degradation shows drug stability, which is a function of the oxidizer concentration and the stabilizer concentration. The results showed that for INH degradation reaction with the addition of GA as stabilizer and the presence of H2O2 as oxidizer, the kinetic parameters obtained were k3 = 1,05 10-4 day-1, kw = 538,95 mM, KA = 0,71 mM, and KB = 11,01 mM-1.

Abstrak :
Penyakit Tuberkulosis merupakan salah satu penyakit yang menjadi salah satu permasalahan di negara berkembang, salah satunya di Indonesia. Terapi tuberkulosis yang biasanya dominan dalam administrasi oral memiliki berbagai permasalahan, yaitu salah satunya adalah rendahnya konsentrasi obat pada tempat infeksi Mycobacterium tuberculosis, yaitu di alveolus.Penghantaran obat antituberculosis langsung ke paru-paru merupakan salah satu strategi untuk meningkatkan konsentrasi obat di lokasi infeksi sehingga efektivitas terapi meningkat. Isoniazid merupakan salah satu lini terapi pertama terapi tuberkulosis. Namun, serbuk isoniazid perlu memiliki sifat arodinamis yang baik agar dapat terdeposisi di paru-paru. Penelitian ini bertujuan untuk mengkaji pengaruh eksipien L-leusin dan/atau amonium bikarbonat terhadap sifat aerodinamis dan profil pelepasan obat serbuk inhalasi isoniazid. Semua formula serbuk inhalasi isoniazid dibuat dengan metode semprot kering. Serbuk inhalasi yang diperoleh kemudian dikarakterisasi morfologi, kandungan lembab, densitas bulk, distribusi ukuran partikel, sifat aerodinamis, gugus fungsi, kadar, serta profil pelepasan dalam medium simulasi paru-paru. Hasil penelitian menunjukkan bahwa penambahan L-leusin meningkatkan sifat aerodinamis, sementara penambahan amonium bikarbonat tidak meningkatkan sifat aerodinamis secara signifikan. Formula serbuk inhalasi isoniazid dengan kombinasi eksipien L-leusin dan amonium bikarbonat memiliki sifat aerodinamis paling baik dengan nilai persentase emitted fraction (EF) 62,08%±1,80 dan fine particle fraction (FPF) 50,39%±6,13 dan diameter aerodinamis (MMAD) 5,68±0,35 µm. Uji pelepasan obat secara in-vitro menunjukkan bahwa semua formula dapat terdisolusi hingga 100% dalam waktu 45 menit. Namun, penambahan amonium bikarbonat tidak mampu mengubah morfologi serbuk inhalasi isoniazid menjadi berpori seperti yang diharapkan. Oleh karena itu, optimasi parameter proses penyemprotan diperlukan untuk menghasilkan partikel dengan pori. ......Tuberculosis is a major health problem in many developing countries, including Indonesia. The therapy for tuberculosis primarily consists of orally consumed drugs, which can result in several issues, including low concentration of antibiotics at the alveoli, the primary site of infection of Mycobacterium tuberculosis. Pulmonary delivery of anti-tuberculosis drugs is one of strategies to provide adequate concentrations at the site of infection, thus increase effectiveness of therapy. Isoniazid is one of the first-line drugs for tuberculosis therapy. However, isoniazid powder should exhibit good aerodynamic properties to be deposited in the lungs. Thus, this study aimed to examine the effect of L-leucine and/or ammonium bicarbonate on aerodynamic properties and drug release profile of isoniazid inhalation powder. All formulations were produced by spray drying, with or without L-leucine and/or ammonium bicarbonate. The obtained powder was characterized by its morphology, moisture content, bulk density, particle size distribution, aerodynamic properties, functional group, content assay, and drug release profile in simulated lung medium. The results showed that the addition of L-leucine increased the aerodynamic properties of isoniazid, while the addition of ammonium bicarbonate did not increase the aerodynamic properties significantly. Isoniazid inhalation powder with combination of 5% w/w L-leucine and 5% w/w ammonium bicarbonate exhibited the best aerodynamic properties with emitted fraction (EF) 62.08%±1.80% and fine particle fraction (FPF) 50.39%±6.13%, and aerodynamic diameter (MMAD) 5.68±0.35 µm. In-vitro drug release test showed that isoniazid in all formulations can be dissolved up to 100% within 45 minutes. However, the addition of ammonium bicarbonate could not form large porous particles as expected. Therefore, further research is required to optimize spray drying parameters in order to achieve the desired particles.