Preformulation Studies In Pharmaceutical Product Development

Preformulation is a branch of pharmaceutical sciences that utilize biopharmaceutical principles in the determination of physicochemical properties of drug substance. It is the first step in the rational development of dosage forms of a drug substance. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients.

Preformulation studies constitute the delicate connection between the two major groups of scientists that is those at the drug discovery end and those at the drug delivery end. It is for the drug discovery group to bring out a novel molecule. In drug discovery, the scientists identifies interesting drug compounds, drug target and delivery mechanism with the potential for development into products,characterize compound and their targets and also provide fundamental information on target biological system.

Drug discovery involve synthesis and extraction which is the process of identifying new molecules. After that, the chemical entity discovered enter biological screening and pharmacological testing to explore the pharmacological activity and therapeutic potential of compounds. Then the drug enter preclinical testing which involve toxicology and safety testing to determine the potential risk a compound poses to humans and the environment,involve use of animals, tissue culture or other test system. Preclinical drug development provide data on the safety and efficacy of the product.

Subsequently, the drug enter preformulation studies. The goals of preformulation studies are to choose correct form of drug substance, evaluate physical properties and generate a thorough understanding of the material’s stability under various conditions, leading to optimal drug delivery system.Steps in preformulation process of pharmaceutical research are evaluating stability, physicochemical properties, mechanical properties, dissolution properties, plasma protein binding and excipients compatibility.

In preformulation process,stability test is done to evaluate drug stability at elevated temperature,on exposure to light and humidity for solid state while for solution, the drug is tested in term of its stability in solvent, stability at varying pH range and also stability to the light. This stabilty data will be used in designing dosage form or formulation which is said to be stable and meet expected specification for identifying, purity, quality and strength throughout their defined storage period at specific storage condition.

Physicochemical properties of drugs are also evaluated such as the molecular structure and weight, color, odour, particle size,shape and cristallinity as well as melting point. Thermal analysis profile of drug is determined to measure the changes in chemical and physical properties of a sample as a function of temperature and the test employ thermogravimetry, differential scanning calorimetry or differential thermal analysis method.

Besides that, the hygroscopic potential of drug and the absorbance spectra using UV and IR is also determined. Next the solubility profile of drug is established as solubility is important for drug dissolution and subsequent absorption. It will affect the bioavailabilty of dosage form besides the ionisation constant and partition coefficient. The last aspect of physichochemical properties is polymorphism. Polymorphism is the ability of solid material to exist in more than one crystalline structure. Polymorphism will affect the stability of drug as drug with different polymorph has different physical and chemical properties and this will cause change in solubility and affect bioavailability. Many physicochemical properties change with the change in internal structure for example melting point, hardness, optical density, crystal shape, vapor pressure and et cetera.

After physicochemical properties, mechanical properties of drug is also determined such as the bulk density, compressibility and powder flow. This data will aid in designing solid dosage form later on in formulation aspect. Other than thats,steps in preformulation are to studies the dissolution properties, plasma protein binding and excipient compatibility of the drug. Dissolution properties will influence the bioavailability of drug while excipient compatibility study is crucial to aid the formulation scientist to determine the best excipients to be used in the formulation of drug to ensure the stability of the finished product.

Formulation group has the task to make the drug into deliverable form with the aid of the data provided by the preformulation scientists. Drug formulation involve the combination of drug substance or active ingredients with drugs excipients to get the desired drug products. Drug excipients are any inactive ingredient that is intentionally added to therapeutic product but not intended to exert therapeutic effects at the intended dosage. It is added to aid drug manufacturing process and to maintain drug stability. The desired drug product is then scaled up to be produced in large quantity.

The drug products then enter phase I,II and III clinical trials to astablish its safety, effectiveness, side effects,toxicity and the most appropriate dosage regimen by testing it in healthy volunteers and patient with the disorder being studied but before the drug is tested in human, the manufacturer must obtain and Investigational New Drug (IND) designation from FDA and the application is based on pre-clinical test data conducted in animal.. After the drug product has passed stage III clinical trial, the drug need to be registered through New Drug Application (NDA) or Biologics License Application.

Once the drug is approved and registered by FDA, it can be marketed but the clinical trial still continue in stage IV or post-marketing surveillance to identify any problems that did not occur in phase I,II or III, such as those that take a long time to appear and those that rarely occur.

Poyo or confident?

Yesterday I presented my ko-k activity and it was my second time presenting in Malay  in this 3 years of my study. I realise that it was very difficult to present in Malay compared to English, it seems to be difficult to find the correct word and speak proper Malay at the same time, if I could present in my Northern accent then it would have been a different story. Then I suddenly realised, do I speak English better than Malay nowadays? Haha. Poyo tak? Haha.

p/s: This is not 'poyo'. I would rather call it high self esteem! :P

Learn to dance in the rain

Many a time we wait for the time to pass to solve the problem but like it or not, our life has been charted with more problems to come after the existing one. So instead of waiting for the storm to pass, its better to learn how to dance in the rain. If you can find a path with no obstacle, it probably does'nt lead anywhere.

p/s: my friend used to tell me that life would be dull without adversities. There's some truth in it. 

Kadang-kadang

Kadang-kadang kita rasa diri kita je bagus, orang lain sume salah. 

Kadang-kadang orang buat baik kat kita banyak, kita tak ingat,tapi dia buat silap sikit je, kita ingat sampai mati.

Kadang-kadang orang tersilap sikit je kita rasa marah gile, tapi bila kita yg buat silap, takpe pulak.

Kadang-kadang kita tunggu orang 10 minit,kita geram, tapi bila orang tunggu kita sejam lebih, pun masih takpe.

Kadang-kadang kita senang je mengutuk orang macam-macam, sedangkan kadang-kadang apa yg kita buat lagi teruk daripada apa yg orang tu buat silap.

Selalu kita nampak kekurangan yg ada pada orang tapi kekurangan pada diri selalu kita rasionalkan dengan macam-macam alasan.

Kadang-kadang, cuma kadang-kadang terpikir, kenapa kita macam ni? Kadang-kadang.

Lesson: Always be lazy

Story About My Mom : Asam pedas vs Tengkuk ayam

Time darjah 3:
Memori aku memang kuat mengingat masa silam. (Well kakak aku cakap aku ni memang nostalgik cket)Time tu keadaan keluarga agak susah dan sesak sikit. Semua tanggungjawab terpikul atas bahu mak yg sabar membesarkan 6 org anak time tu kakak sulung baru form 3, adik bongsu plak darjah 1. Memang sesaklah waktu tu, jarang2 makan nasik malam. Kerap kali  sekadar makan cucur bawang mak buat makan petang dalam pukul 6 pm macam tu dan malam kalau lapar sangat makan biskut kering atau roti benggali cicah teh.

 Makan malam pun kalau ada lauk mak masak tengahhari yg lebih, lauk tu la makan sorang sikit. Ada satu hari tu mak masak asam pedas ikan pari yg memang feveret aku (time tu bagi kami lauk ni memang mewah). Malam tu ada la lebih kuah asam pedas tu sikit. Aku ni plak yg memang kuat makan pun merengek lapar malam tu. Mak pun kikis saki baki kerak nasi dalam periuk dan masukkan dalam satu pinggan, letak kuah asam pedas pastu panggil aku dgn leh (adik bongsu aku) makan. Sedap sungguh nasik tu aku ingat sampai sekarang, mak aku tengok ja aku dgn adik aku makan dengan muka yg sedih. Adik aku makan sikit ja pastu dia taknak, aku pun sengaja berhenti makan tinggalkan saki baki dalam sesuap. Mak aku suruh habiskan tapi aku cakap kenyang, sedangkan saja aku tinggal untuk mak makan. Lepas tu kami pun buat kerja masing2, mak plak lepas habis basuh pinggan dan solat isyak, mak suka duduk atas buaian kat luar rumah  berzikir perlahan sambil melihat kadang2 orang lalu-lalang. Aku tahu mak sedih, tapi hanya itu yang mampu mak lakukan selepas sehari melayan kami, dia hanya mampu duduk diatas buaian mengenangkan nasib kami semua. Kadang2 mak menangis perlahan. Malam tu aku bisikkan pada hatiku, bila aku dah kerja dan senang nanti, takkan aku biarkan satu malam berlalu di mana mak sedih atau lapar.

Tahun 3 university:

Aku balik rumah, cuti. Aku sibuk study, next week ada 2 test & pbl (problem based learning). Mak mintak tolong aku belek2 resit, kirakan berapa banyak yg dah bayar utk rumah yg mak dah beli. Aku pun kira pastu aku bebal sebab resit tu dah bercampur2 ada yg 1 payment tp 2 resit. Lepas tu aku sambung study. Mak cakap lagi pasal resit2 tu. Dengan suara sedikit meninggi ku cakap "Time hanip study janganla cakap pasal duit, tension la!" Mak aku hanya senyap. Dalam hati aku rasa bersalah meninggi suara tadi. Dalam pukul 6 lebih mak ke dapur, "mak tanya malam ni nak makan tak hanip?" Aku jawab " kalau ada lauk hanip makan la".


Pastu aku ke dapur, mak sendukkan nasi tengah hari td dari rice cooker (sebab nak masak nasik lagi). Aku pun amik sikit nasik tengah hari tadi, aku tanya mak ada lauk tak. Mak cakap "Ada tu mak tinggal kat ampa sorang seketul ayam jangan amik lebih nanti tak cukup, mak pun amik tengkuk ja" Aku pandang semangkuk ayam masak merah tengah hari tadi yg memang mak masak special setiap kali aku balik sebab ni ayam masak merah pun feveret aku gak sejak kecik.


Aku tengok dalam pinggan mak ada nasik, 1 tengkuk ayam dan sedikit kuah. Aku pun amik seketul ayam yang paling kecik sekali, pastu sambil makan aku teringat balik cerita time aku darjah 3 tadi tu. Dalam hati rasa sebak, sambil aku makan pelan2 aku tengok muka mak berulang kali. Masa dah berlalu, tapi kasih sayang mak pada anak dia tak pernah berubah, aku pulak semakin besar semakin lupa kat mak aku, duk kat kl tu bila nak exam atau ada masalah baru teringat nak telefon mak. Harap Allah beri kesempatan untuk aku balas jasa mak aku dan buat mak aku senang. Hanip mintak maaf mak.....

Geram

Cerita 1:

Hari ni pi fotostat buku, tinggal la kat kedai tu.. Dia suruh ambik malam, tapi dah 2 kali p kedai tu tutup, kat pintu kedai ada number phone, try call owner tu berkali2 dia tak jawab. Hati rasa geram, kalau nak berniaga menyusahkan orang lebih baik jgn berniaga. Esok dah nak balik penang, kalau kedai tu tak bukak esok nampak gayanya kena amik minggu depan la tapi minggu depan exam.

Cerita 2:

Pagi tadi p hiking di bukit broga, p bertiga, aku yang ajak. Ada sorang member ni dia asyik mengeluh je keje. Ada je yg nak dicomplainnye sepanjang jalan. "Tak cantik la tempat ni, menyesal la datang, korang ni mcm ni la, mcm tu la." Kalau ikutkan hati rase mcm nak tolak je masuk gaung tu, merosakkan mood orang je dah la pagi2 sebelum subuh time tu, kalau ko x suke jangan la datang. Dalam hati ni membara je tapi just senyap je la (When i m silent, there is something wrong). Pastu teringat pesan en azhar (pegawai jabatan kebajikan msyrkt di rumah seri kenangan cheras tempat buat ko-k), dia cakap kita kena selalu maafkan kawan. Jadi sabar je la, pas beberapa lama cakap la balik, senyum je walau dalam hati agak sakit.

Cerita 3:

Takde ape2 cerita dah... Cuma sejak kebelakangan ni rasa asyik nak marah orang je keje tapi senyap je la cuma waktu time2 mood x menentu ni sape yg cari pasal mmg aku tarik muka je la.